WO2024166131A1

WO2024166131A1 - Heteroaryl compounds as pkmyt1 inhibitors

Info

Publication number: WO2024166131A1
Application number: PCT/IN2024/050118
Authority: WO
Inventors: Navnath Popat Karche; Sukanya Patra
Original assignee: Satyarx Pharma Innovations Private Ltd
Current assignee: Satyarx Pharma Innovations Private Ltd
Priority date: 2023-02-09
Filing date: 2024-02-07
Publication date: 2024-08-15
Anticipated expiration: 2025-08-09
Also published as: TW202440574A

Abstract

The present invention relates to novel heteroaryl compounds of Formula (I) and their pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including other possible isotopes thereof as inhibitors of PKMYT1 The present invention also provides the process of preparation of compounds of Formula (I) for treating cancer.

Description

HETEROARYL COMPOUNDS AS PKMYT1 INHIBITORS RELATED PATENT APPLICATION: This application claims the priority to, and benefit of Indian Patent Application No. 202341008447 filed on February 09, 2023, and Indian Patent Application No. 202341053729 filed on August 10, 2023; the disclosures of which are incorporated herein by reference. FIELD OF THE INVENTION: The present invention relates to novel heteroaryl compounds of Formula (I) as inhibitors of PKMYT1, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including their isotopes thereof.

The present invention also relates to a process for the manufacture of novel heteroaryl compounds of Formula (I), pharmaceutical compositions containing them, and their use in treatment of cancer. BACKGROUND OF THE INVENTION: Cellular DNA is constantly exposed to various endogenous and exogenous damages and therefore needs repair in order to progress through the cell cycle and undergo cellular proliferation. Multiple proteins co-ordinate and work in concert to progress through various sophisticated signaling pathways called DNA damage response (DDR). The DDR and checkpoint pathways are intertwined signaling networks that arrest cell cycle, recognize and repair genetic mistakes (Curr Cancer Drug Targets, 2012 May;12(4):356-71). Majority of cancers do not have properly functional G1/S checkpoint and are thus more dependent on effective G2 checkpoint (Cell Prolif. 2000, 33, 261-274). PKMYT1 (membrane-associated tyrosine- and threonine- specific cdc2-inhibitory kinase) functions as negative regulator of CDK1 (cyclin- dependent kinase 1) and leads to G2/M checkpoint cell cycle arrest. (Nature, Vol. 604, April 28, 2022) Inhibiting its function leads to unscheduled activation of CDK1 selectively in CCNE1-overexpressing cells. This promotes early mitosis in cells undergoing DNA synthesis and eventual cell death via apoptosis (Journal of Hematology & Oncology (2020) 13:126). CRISPR screening confirms that CCNE1 overexpressed cells are dependent on PKMYT1 function (Journal of Hematology & Oncology (2020) 13:126). In ovarian cancer, CCNE1 amplification was detected in about 20% of tumours (Nature, 2015, 521, 489-494; Clin. Cancer Res.2009, 15, 1417-1427). The CCNE1 amplified tumors have poor prognosis and very limited treatment options (Curr. Opin. Obstet. Gynecol., 2017, 29, 26-34, J. Med. Chem.2022, 65, 15, 10251- 10284). Cyclin E itself is considered to be an undruggable target due to its essential role in cell cycle, but its cognate cyclin-dependent kinase CDK2 is druggable. CDK2 inhibition shows promising activity in CCNE1-amplified cell lines (Clin. Cancer Res., 2013, 19, 5960-5971) and selective CDK2 inhibitors are starting to enter clinical development. However, emergence of resistance to CDK inhibitors needs evaluation of other novel therapeutic targets like PKMYT1. Selective PKMYT1 inhibitors are being designed particularly for treatment of CCNE1 amplified cancer patients. PCT international Application Publication No. WO2021/195781 discloses different compounds for use against PKMYT1.

As compounds having a PKMYT1 inhibitory effect, for example, compounds disclosed in the following publications are also known: WO2023/155870, WO2023/155871, WO2023/155892, WO2023/174329, WO2023/174397, WO2023/198199, WO2023/220831, WO2023/249563, US2023/0122909, and US2023/0142913. Despite the existing known compounds, there is a need to develop novel and more efficient PKMYT1 inhibitors as anti-cancer drug that could efficiently provide targeted treatments against cancer. OBJECTS OF THE INVENTION: The primary object of the present invention is to provide novel heteroaryl compounds of Formula (I) as PKMYT1 inhibitor. Another object of the invention is to provide pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical & geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, of the novel heteroaryl compounds of Formula (I). Yet another object of the present invention is to provide a process for the preparation of novel heteroaryl compounds of Formula (I). Another object of the present invention is to prepare a pharmaceutical composition comprising the heteroaryl compounds of Formula (I). Yet another object of the present invention is to provide a method of treating cancer by using the composition comprising novel heteroaryl compounds of Formula (I). SUMMARY OF THE INVENTION: Accordingly, the present invention provides novel heteroaryl compounds as shown below. Heteroaryl compounds of Formula (I)

wherein, ring A is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- 5 to 6 membered heteroaryl, substituted- or unsubstituted- 5 to 8 membered carbocycle, and substituted- or unsubstituted- 5 to 8 membered heterocycle; X and Y are independently selected from -N or -CR⁶; R¹ and R² are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- heteroaryl, alkenyl, -NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, -C(=O)N(R^7b)₂, and -N(R^7b)₂, or R¹ and R² together can form a substituted- or unsubstituted- 5-8 membered heterocycle; R³ and R⁴ are independently selected from cyano, substituted- or unsubstituted- heteroaryl, -NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, -C(=O)N(R^7b)₂, and -N(R^7b)₂, or R³ and R⁴ together can form a substituted- or unsubstituted- 5-8 membered heterocycle, or substituted- or unsubstituted- 5-6 membered heteroaryl; R⁵ is selected from hydrogen, hydroxy, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, - NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, -C(=O)N(R^7b)2, and -N(R^7b)₂; R⁶ is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle and - N(R^7b)₂; R^7a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, and substituted- or unsubstituted- heterocycle; R^7b is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, and substituted- or unsubstituted- heterocycle; n is an integer selected from 1-5; and when R¹ and R² together is not a substituted- or unsubstituted- 5-8 membered heterocycle and R³ and R⁴ together is not a substituted- or unsubstituted- 5-8 membered heterocycle or substituted- or unsubstituted- 5-6 membered heteroaryl, then n is 2 or >2, and R^7b is hydrogen when -OR^7b is part of R⁵; or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof. The compounds of Formula (I) as defined above, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein ring A is selected from substituted- or unsubstituted- aryl or substituted- or unsubstituted- 5 to 6 membered heteroaryl. The compounds of Formula (IA) are represented by the structure:

wherein, ring A is phenyl; X is N, Y is -CH-; R¹ and R² are methyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-8 membered heterocycle, or substituted- or unsubstituted- 5-6 membered heteroaryl; and R⁵ and n are each the same as defined in compound of Formula (I); or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof. The compounds of Formula (IA) are represented by the structure:

ring A is phenyl; X is N, Y is -CH-; R¹ is methyl; R² is cycloalkyl or heterocycle or heteroaryl or OR^7b, wherein R^7b alkyl or cycloalkyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-6 membered heteroaryl; and R⁵ and n are each the same as defined in compound of Formula (I); or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof. The compounds of Formula (IA) represented by the structure:

wherein, ring A is phenyl; X is N, Y is -CH-; R¹ is cycloalkyl or heterocycle or OR^7b, wherein R^7b is alkyl or cycloalkyl; R² is methyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-6 membered heteroaryl; and R⁵ and n are each the same as defined in compound of Formula (I); or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof. The compounds of Formula (IA) are represented by the structure:

wherein, ring A is phenyl; X is N, Y is -CH-; R¹ is methyl; R² is substituted alkyl, wherein substituent is -OR^8b; R^8b is selected from hydrogen, alkyl, haloalkyl, and cycloalkyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-6 membered heteroaryl; and R⁵ and n are each the same as defined in compound of Formula (I); or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof. The compounds of Formula (IB) are represented by the structure:

wherein, ring A is phenyl; X is N, Y is -CH-; R¹ and R² are methyl; R³ is -C(=O)N(R^7b)2, and R⁴ is -N(R^7b)2, wherein R^7b is hydrogen; and R⁵ and n are each the same as defined in compound of Formula (I); or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof. The compounds of Formula (IC) and Formula (ID) are represented by the structure:

wherein Y is N or CR⁶; R¹ and R² are independently hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- heteroaryl, alkenyl, - NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, -C(=O)N(R^7b)₂, or -N(R^7b)₂; R^5a is C1-4-alkyl or halogen; R^5b is hydrogen, C1-4-alkyl, or halogen; R^5c is hydroxy; R^5d is hydrogen or hydroxy; R⁶ is hydrogen, halogen, or C1-4-alkyl; R^7a is substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, or substituted- or unsubstituted- heterocycle; and R^7b is hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, or substituted- or unsubstituted- heterocycle; or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof. The compounds of Formula (IC) and Formula (ID) as defined above, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein Y is CR⁶; R¹ and R² are independently hydrogen; halogen; nitro; cyano; C1-4-alkyl optionally substituted with one or more groups selected from the group consisting of halogen, -O-R^8b, -N(H)R⁸, -N(alkyl)R⁸, C_3-6-cycloalkyl, and heterocycle, in which said C_3-6- cycloalkyl and heterocycle may be further substituted with one or more groups selected from the group consisting of halogen, cyano, C1-4-alkyl, -O-R^8b, C1-4- haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; C_3-6-cycloalkyl optionally substituted with one or more groups selected from the group consisting of halogen, cyano, C1-4- alkyl, -O-R^8b, C1-4-haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; heterocycle optionally substituted with one or more groups selected from the group consisting of halogen, cyano, -O-R^8b, C_1-4-alkyl, -CH₂-OR^8b, C_1-4-haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; heteroaryl optionally substituted with one or more groups selected from the group consisting of halogen, cyano, C1-4-alkyl, -O-(C1-4-alkyl), C1-4-haloalkyl, -O-(C1-4- haloalkyl), -N(alkyl)alkyl, -N(H)alkyl, and -NH₂; C_2-4 alkenyl; -OR^7b; or -N(R^7b)₂; R^7b is hydrogen; C3-6-cycloalkyl; or C1-4-alkyl optionally substituted with one or more groups selected from the group consisting of halogen and C3-6-cycloalkyl; R⁸ is hydrogen, C_1-4-alkyl, or C_3-6-cycloalkyl; and R^8b is hydrogen, C_1-4-alkyl, C_1-4-haloalkyl, or C_3-6-cycloalkyl. The compounds of Formula (IC) and Formula (ID) as defined above, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein: R¹ and R² are independently hydrogen; halogen; nitro; cyano; C_1-4-alkyl optionally substituted with one or more groups selected from the group consisting of halogen, -O-R^8b, -N(H)R⁸, -N(alkyl)R⁸, C_3-6-cycloalkyl, piperidinyl, pyrrolidinyl, and morpholinyl, in which said C_3-6-cycloalkyl, piperidinyl, pyrrolidinyl, and morpholinyl may be further substituted with one or more groups selected from the group consisting of halogen, cyano, -O-R^8b, C1-4-alkyl, C1-4-haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; C_3-6-cycloalkyl optionally substituted with one or more groups selected from the group consisting of halogen, cyano, -O-R^8b, C_1-4-alkyl, C_1-4- haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; piperidinyl, pyrrolidinyl, morpholinyl, or 6- azaspiro[2.5]octyl, each of which may be substituted with one or more groups selected from the group consisting of halogen, cyano, -O-R^8b, C_1-4-alkyl, -CH₂- OR^8b, C1-4-haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; pyrazolyl optionally substituted with one or more groups selected from the group consisting of halogen, cyano, C1- ₄-alkyl, -O-(C_1-4-alkyl), C_1-4-haloalkyl, -O-(C_1-4-haloalkyl), -N(alkyl)alkyl, - N(H)alkyl, and -NH2; C2-4 alkenyl; -OR^7b; or -N(R^7b)2; R^7b is hydrogen; C3-6-cycloalkyl; or C1-4-alkyl optionally substituted with one or more groups selected from the group consisting of halogen and C_3-6-cycloalkyl; R⁸ is hydrogen, C1-4-alkyl, or C3-6-cycloalkyl; and R^8b is hydrogen, C1-4-alkyl, C1-4-haloalkyl, or C3-6-cycloalkyl. The compound of Formula (I), or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein the compounds are selected from the group consisting of:

The present invention provides a process for preparing heteroaryl compounds of Formula (I)

wherein, ring A is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- 5 to 6 membered heteroaryl, substituted- or unsubstituted- 5 to 8 membered carbocycle, and substituted- or unsubstituted- 5 to 8 membered heterocycle; X and Y are independently selected from -N or -CR⁶; R¹ and R² are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- heteroaryl, alkenyl, -NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, -C(=O)N(R^7b)2, and -N(R^7b)2, or R¹ and R² together can form a substituted- or unsubstituted- 5-8 membered heterocycle; R³ and R⁴ are independently selected from cyano, substituted- or unsubstituted- heteroaryl, -NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, -C(=O)N(R^7b)₂, and -N(R^7b)₂, or R³ and R⁴ together can form a substituted- or unsubstituted- 5-8 membered heterocycle, or substituted- or unsubstituted- 5-6 membered heteroaryl; R⁵ is selected from hydrogen, hydroxy, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, - NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, -C(=O)N(R^7b)2, and -N(R^7b)2; R⁶ is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle and - N(R^7b)2; R^7a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, and substituted- or unsubstituted- heterocycle; R^7b is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, and substituted- or unsubstituted- heterocycle; R^8b is selected from hydrogen, alkyl, haloalkyl, and cycloalkyl; n is an integer selected from 1-5; and when R¹ and R² together is not a substituted- or unsubstituted- 5-8 membered heterocycle and R³ and R⁴ together is not a substituted- or unsubstituted- 5-8 membered heterocycle or substituted- or unsubstituted- 5-6 membered heteroaryl, then n is 2 or >2, and R^7b is hydrogen when -OR^7b is part of R⁵; or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof comprising the steps of: i) treating starting compound (a) with compound (d)

in presence of a base, a catalyst and a solvent to obtain compound (b);

ii) treating the compound (b) of step i) with nitrile in presence of a base, a catalyst and a solvent to obtain compound (c);

iii) treating the compound (c) of step (ii) with a reagent to obtain heteroaryl compounds of Formula (I) or heterocycles; and iv) optionally, subjecting compound (c) of step (ii) to deprotection of protecting group to obtain the compounds of Formula (I); wherein the compounds of Formula (I) are compounds of Formula (IA) or compounds of Formula (IB) or compounds of Formula (IC) or compounds of Formula (ID). The process as above wherein the base in step (i) is selected from a group comprising of sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, ammonium hydroxide, potassium carbonate, potassium bicarbonate and magnesium carbonate, wherein the preferred base is caesium carbonate. The process as above, wherein the catalyst in step (i) is selected from the group comprising of Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis (triphenylphosphine)palladium(0) and tris(dibenzylideneacetone) dipalladium(0), wherein the preferred catalyst is Tris(dibenzylideneacetone)dipalladium(0). The process as above, wherein the solvent in step (i) is selected from the group comprising of diethyl ether, dimethylformamide tetrahydrofuran, dichloromethane, methanol, DMSO, dimethoxy ethane, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol, acetonitrile and diisopropyl ether, wherein the preferred solvent is 1,2-dimethoxy ethane. The process as above, wherein the nitrile in step (ii) is selected from a group comprising of malononitrile, propionitrile and ethanenitrile, benzonitrile, wherein the preferred nitrile is malononitrile. The process as above, wherein the base in step (ii) is selected from a group comprising of sodium tertiary butoxide, sodium hydride, lithium hydride, ammonium hydroxide, potassium hydride, rubidium hydride, caesium hydride or lithium aluminium hydride, wherein the preferred base is sodium tertiary butoxide, sodium bicarbonate, or sodium hydride. The process as above, wherein the catalyst in step (ii) is selected from a group comprising Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) and tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Bis(diphenylphosphino)ferrocene]dichloropalladium(II). The process as above, wherein the solvent in step (ii) is selected from a group comprising of DMSO, 1,2-dimethoxy ethane, methanol, dichloromethane, toluene, dimethylformamide, tetrahydrofuran, diethyl ether and chlorinated solvent, wherein the preferred solvent is 1,2-dimethoxy ethane. The process as above, wherein the reagent in step (iii) is selected from a group comprising of formamide, ethyl acetate, ethyl carbonate and guanidine hydrochloride. The present invention provides a pharmaceutical composition comprising the above compounds, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, and a pharmaceutically acceptable excipient or carrier. The present invention provides use of above compounds or a pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof for manufacturing a medicament for a treatment of a cancer associated with PKMYT1 protein. The present invention provides use of above compounds or a pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof for a treatment of a cancer associated with PKMYT1 protein. The present invention provides the compounds as above, or a pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof for a treatment of a cancer associated with PKMYT1 protein. The present invention provides a method of inhibiting PKMYT1 protein comprising administering to a cancer subject therapeutically effective amount of a pharmaceutical composition comprising at least one of the compounds as defined above, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein the said method for treatment of cancer is associated with PKMYT1 protein. The method as above wherein the cancer depends on the activity of PKMYT1, wherein the cancer overexpresses CCNE1. The method as above, wherein the cancer has an inactivating mutation in the FBXW7 and PPP2R1A genes, wherein the cancer is a solid tumor. The method as above, wherein the cancer is breast cancer, colorectal cancer, endometrial cancer, esophageal cancer, glioblastoma, hepatocellular carcinoma, lung cancer, neuroblastoma, ovarian cancer, prostate cancer, stomach cancer, or uterine cancer. DETAILED DESCRIPTION OF THE INVENTION: Embodiments described herein can be understood more readily by reference to the following detailed description, examples, and tables. Numerous modifications and adaptations will be readily apparent to those skilled in the art without departing from the spirit and scope of the invention. Disclosed herein is the detailed description of the present invention pertaining to novel heteroaryl compounds of Formula (I) and pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof. General terms used in Formula (I) can be defined as follows; however, the meaning stated should not be interpreted as limiting the scope of the term per se. The term “halogen” or “halo” means fluorine or fluoro (F), chlorine or chloro (Cl), bromine or bromo (Br), or iodine or iodo (I). The term ‘alkyl’ refers to an alkane derived hydrocarbon radical that includes solely carbon and hydrogen atoms in the backbone, contains no unsaturation, has carbon atoms from one to six, i.e. C_1-6, preferably carbon atoms from one to four, i.e. C_1-4, and is attached to the remainder of the molecule by a single bond, e.g., methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, 1,1-dimethylethyl (tert-butyl) and the like. As used herein, a “C_1-4-alkyl” group means a radical having from 1 to 4 carbon atoms in a linear or branched arrangement, and includes methyl, ethyl, propyl, isopropyl, n-butyl, 1-methylpropyl, 2-methylpropyl, and tert-butyl. Unless set forth or recited to the contrary, all alkyl groups described or claimed herein may be straight chain or branched, substituted or unsubstituted. When ‘alkyl’ such as C_1-4-alkyl is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (=O), cyano, halogen, haloalkyl, cycloalkyl, substituted- or unsubstituted- aryl, substituted- or unsubstituted- heterocycle, -OR^8b, -SO2R^8a, -C(=O)OR^8b, -OC(=O)R^8a, -OC(=O)OR^8a, - C(=O)N(H)R⁸, -C(=O)N(alkyl)R⁸, -N(H)C(=O)R^8a, -N(H)R⁸, and -N(alkyl)R⁸. The term ‘alkenyl’ refers to an alkene derived hydrocarbon radical that includes solely carbon and hydrogen atoms in the backbone, contains one or more double bonds, has carbon atoms from two to six, i.e. C_2-6, preferably carbon atoms from two to four, i.e. C2-4, and is attached to the remainder of the molecule by a single bond, e.g., vinyl, allyl, prop-1-en-2-yl, but-3-en-1-yl, but-2-en-1-yl, but-1-en-2-yl, pent-4-en-1-yl, hex-5-en-1-yl, and the like. As used herein, a “C_2-4-alkenyl” group means a radical having from 2 to 4 carbon atoms in a linear or branched arrangement, and includes, but is not limited to, vinyl, allyl, prop-1-en-2-yl, and but-3-en-1-yl. The term ‘haloalkyl’ means alkyl substituted with one or more halogen atoms and includes perhaloalkyl wherein all the hydrogen atoms of the said alkyl group are substituted with halogen. For example, “C1-4-haloalkyl” includes, but is not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, bromomethyl, fluoroethyl, difluoroethyl, pentafluoroethyl, dichloroethyl, and chloropropyl. In one aspect, an example of C_1-4-haloalkyl includes difluoromethyl or trifluoromethyl, and in another aspect, an example of C1-4-haloalkyl includes trifluoromethyl. The term ‘carbocycle’ or ‘cycloalkyl’ refers to a non-aromatic mono or multicyclic ring system having 3 to 12 carbon atoms, i.e. C3-12, preferably carbon atoms from 3 to 6, i.e. C_3-6, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like. For example, “C_3-6-cycloalkyl” includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Unless set forth or recited to the contrary, all cycloalkyl groups described or claimed herein may be substituted or unsubstituted. As used herein, a “5 to 8 membered carbocycle” group includes, but is not limited to, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. When ‘carbocycle’ or ‘cycloalkyl’ such as C_3-6-cycloalkyl is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (=O), cyano, halogen, alkyl, haloalkyl, -OR^8b, -SO2R^8a, -C(=O)OR^8b, -OC(=O)R^8a, - OC(=O)OR^8a, -C(=O)N(H)R⁸, -C(=O)N(alkyl)R⁸, -N(H)C(=O)R^8a, -N(H)R⁸, and - N(alkyl)R⁸. The term ‘aryl’, as used herein, refers to a monovalent monocyclic, bicyclic or tricyclic aromatic hydrocarbon ring system. Examples of aryl groups include phenyl, naphthyl, anthracenyl, fluorenyl, indenyl, azulenyl, and the like. In one aspect, an example of aryl includes phenyl or naphthyl, and in another aspect, an example of aryl includes phenyl. When the ‘aryl’ group is substituted, it is substituted with 1 to 4 substituents selected from halogen, alkyl, cyano, haloalkyl, cycloalkyl, -O-alkyl, -O-haloalkyl, -O-C(=O)-aryl, -N(alkyl)alkyl, -N(H)alkyl, -NH2, -N(alkyl)C(=O)alkyl, - N(H)C(=O)alkyl, -C(=O)N(alkyl)alkyl, -C(=O)N(H)alkyl, -C(=O)NH2, - SO₂N(alkyl)alkyl, -SO₂N(H)alkyl, -SO₂NH₂, -C(=O)OH, -C(=O)-alkyl, and - C(=O)O-alkyl. The term ‘heteroaryl’, as used herein, refers to a 5-14 membered monocyclic, bicyclic, or tricyclic ring system having 1-4 ring heteroatoms selected from O, N, or S, and the remainder ring atoms being carbon (with appropriate hydrogen atoms unless otherwise indicated), wherein at least one ring in the ring system is aromatic. Examples of such heteroaryl groups include pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, furyl, oxazolyl (1,3-oxazolyl), isoxazolyl (1,2-oxazolyl), oxadiazolyl, thienyl, thiazolyl (1,3-thiazolyl), isothiazolyl (1,2-thiazolyl), thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazyl, indolyl, isoindolyl, benzofuryl, benzothienyl, indazolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, quinolyl, isoquinolyl, cinnolinyl, quinazolinyl, quinoxalyl, pyrolopyridyl, and imidazolopyridyl. As used herein, a “5 to 6 membered heteroaryl” group includes, but is not limited to, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, furyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, and pyrazyl. When the ‘heteroaryl’ group is substituted, it is substituted with 1 to 4 substituents selected from halogen, alkyl, cyano, haloalkyl, cycloalkyl, -O-alkyl, O-haloalkyl, -N(alkyl)alkyl, -N(H)alkyl, -NH2, -N(alkyl)C(=O)alkyl, -N(H)C(=O)alkyl, - C(=O)N(alkyl)alkyl, -C(=O)N(H)alkyl, -C(=O)NH₂, -SO₂N(alkyl)alkyl, - SO2N(H)alkyl, -SO2NH2, -C(=O)OH, -C(=O)-alkyl, and -C(=O)O-alkyl. The term ‘heterocycle’, unless otherwise specified, refers to substituted or unsubstituted non-aromatic 3- to 15- membered ring which consists of carbon atoms and with one or more (e.g., 2 or 3) heteroatom(s) independently selected from N, O or S. Examples of a monovalent group of such heterocycle include aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, dihydropyridyl, tetrahydropyridyl, dihydropyridazinyl, tetrahydropyridazinyl, dihydropyrimidinyl, tetrahydropyrimidinyl, dihydropyrazinyl, tetrahydropyrazinyl, oxetanyl, tetrahydrofuryl, dihydrofuryl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, dihydrothiopyranyl, piperazinyl, morpholinyl, thiomorpholinyl, dihydroindolyl, dihydroisoindolyl, dihydrobenzofuryl, dihydroisobenzofuryl, tetrahydrobenzoxazolyl, dihydrofuropyridyl, dihydropyrazolomorpholinyl, pyridinodioxanyl, dihydroazabenzofuryl, dihydroazaisobenzofuryl, dihydroazaindolyl, and 6- azaspiro[2.5]octyl. As used herein, a monovalent group of “5 to 8 membered heterocycle” group includes, but is not limited to, pyrrolidinyl, piperidinyl, dihydropyridyl, tetrahydropyridyl, dihydropyridazinyl, tetrahydropyridazinyl, dihydropyrimidinyl, tetrahydropyrimidinyl, dihydropyrazinyl, tetrahydropyrazinyl, tetrahydrofuryl, dihydrofuryl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, dihydrothiopyranyl, piperazinyl, morpholinyl, thiomorpholinyl, and 6-azaspiro[2.5]octyl. When ‘heterocycle’ is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (=O), cyano, halogen, alkyl, haloalkyl, -OR^8b, - CH2-OR^8b, -C(=O)OR^8b, -OC(=O)R^8a, -OC(=O)OR^8a, -C(=O)N(H)R⁸, - C(=O)N(alkyl)R⁸, -N(H)C(=O)R^8a, -N(H)R⁸, and -N(alkyl)R⁸, two substituents on same or adjacent carbon will form cycloalkyl ring. In the specification and claims, each R⁸ is independently selected from hydrogen, alkyl, and cycloalkyl; each R^8a is independently selected from alkyl, haloalkyl and cycloalkyl; and each R^8b is selected from hydrogen, alkyl, haloalkyl, and cycloalkyl. The term ‘oxo’ means a divalent oxygen (=O) attached to the parent group. For example, oxo attached to carbon forms a carbonyl, oxo substituted on cyclohexane forms a cyclohexanone, and the like. It is to be noted that the compound of Formulas (IA), (IB), (IC) and (ID) is included within the scope of the compound of Formula (I), and accordingly suitable examples or embodiments of the compound of Formulas (IA), (IB), (IC) and (ID) are to be referred to those as exemplified for the compounds of Formula (I). Accordingly in one aspect the present invention provides a compound of Formula (I):

or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, deuterated compounds including isotopes, thereof, wherein: ring A is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- 5 to 6 membered heteroaryl, substituted- or unsubstituted- 5 to 8 membered carbocycle, and substituted- or unsubstituted- 5 to 8 membered heterocycle; X and Y are independently selected from group consisting of -N or -CR⁶; R¹ and R² are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- heteroaryl, alkenyl, -NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, -C(=O)N(R^7b)2, and -N(R^7b)2, or R¹ and R² together can form a substituted- or unsubstituted- 5-8 membered heterocycle; R³ and R⁴ are independently selected from cyano, substituted- or unsubstituted- heteroaryl, -NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, -C(=O)N(R^7b)2, and -N(R^7b)2, or R³ and R⁴ together can form a substituted- or unsubstituted- 5-8 membered heterocycle, or substituted- or unsubstituted- 5-6 membered heteroaryl; R⁵ is selected from hydrogen, hydroxy, halogen, hydroxy, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, - NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, -C(=O)N(R^7b)2, and -N(R^7b)₂; R⁶ is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle and - N(R^7b)₂; R^7a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, and substituted- or unsubstituted- heterocycle; R^7b is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, and substituted- or unsubstituted- heterocycle; n is an integer selected from 1-5; and when R¹ and R² together is not a substituted- or unsubstituted- 5-8 membered heterocycle and R³ and R⁴ together is not a substituted- or unsubstituted- 5-8 membered heterocycle or substituted- or unsubstituted- 5-6 membered heteroaryl, then n is 2 or >2, and R^7b is hydrogen when -OR^7b is part of R⁵. In another embodiment, the present invention provides compound of Formula (1A),

or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein: ring A is phenyl; X is N, Y is -CH-; R¹ and R² are methyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-8 membered heterocycle, or substituted- or unsubstituted- 5-6 membered heteroaryl; and R⁵ and n are each the same as defined in the compound of Formula (I). In yet another embodiment, the present invention provides compound of Formula (IA), wherein: ring A is phenyl; X is N, Y is -CH-; R¹ is methyl; R² is cycloalkyl or heterocycle or heteroaryl or OR^7b, wherein R^7b alkyl or cycloalkyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-6 membered heteroaryl; and R⁵ and n are each the same as defined in the compound of Formula (I). In further embodiment, the present invention provides compound of Formula (IA), wherein: ring A is phenyl; X is N, Y is -CH-; R¹ is cycloalkyl or heterocycle or OR^7b, wherein R^7b alkyl or cycloalkyl; R² is methyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-6 membered heteroaryl; and R⁵ and n are each the same as defined in the compound of Formula (I). In further embodiment, the present invention provides compound of Formula (IA), wherein: ring A is phenyl; X is N, Y is -CH-; R¹ is methyl; R² is substituted alkyl, wherein substituent is -OR^8b; R^8b is selected from hydrogen, alkyl, haloalkyl, and cycloalkyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-6 membered heteroaryl; and R⁵ and n are each the same as defined in the compound of Formula (I).

In yet another embodiment, the present invention provides compound of Formula (IB),

or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes, thereof, wherein: ring A is phenyl; X is N, Y is -CH-; R¹ and R² are methyl; R³ is -C(=O)N(R^7b)2, and R⁴ is -N(R^7b)2, wherein R^7b is hydrogen; and R⁵ and n are each the same as defined in the compound of Formula (I). In another embodiment of the compound of Formula (I), the present invention provides a compound of Formula (IC) and compound of Formula (ID) represented by the structure:

wherein Y is N or CR⁶; R¹ and R² are independently hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- heteroaryl, alkenyl, - NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, -C(=O)N(R^7b)₂, or -N(R^7b)₂; R^5a is C1-4-alkyl or halogen; R^5b is hydrogen, C1-4-alkyl, or halogen; R^5c is hydroxy; R^5d is hydrogen or hydroxy; R⁶ is hydrogen, halogen, or C_1-4-alkyl; R^7a is substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, or substituted- or unsubstituted- heterocycle; and R^7b is hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, or substituted- or unsubstituted- heterocycle; or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof. In another embodiment of the compound of Formula (IC) or compound of Formula (ID), the present invention provides a compound of Formula (IC) and Formula (ID), or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein: Y is CR⁶; R¹ and R² are independently hydrogen; halogen; nitro; cyano; C_1-4-alkyl optionally substituted with one or more groups selected from the group consisting of halogen, -O-R^8b, -N(H)R⁸, -N(alkyl)R⁸, C3-6-cycloalkyl, and heterocycle, in which said C3-6- cycloalkyl and heterocycle may be further substituted with one or more groups selected from the group consisting of halogen, cyano, C1-4-alkyl, -O-R^8b, C1-4- haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; C3-6-cycloalkyl optionally substituted with one or more groups selected from the group consisting of halogen, cyano, C_1-4- alkyl, -O-R^8b, C1-4-haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; heterocycle optionally substituted with one or more groups selected from the group consisting of halogen, cyano, -O-R^8b, C_1-4-alkyl, -CH₂-OR^8b, C_1-4-haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; heteroaryl optionally substituted with one or more groups selected from the group consisting of halogen, cyano, C1-4-alkyl, -O-(C1-4-alkyl), C1-4-haloalkyl, -O-(C1-4- haloalkyl), -N(alkyl)alkyl, -N(H)alkyl, and -NH2; C2-4 alkenyl; -OR^7b; or -N(R^7b)2; R^7b is hydrogen; C3-6-cycloalkyl; or C1-4-alkyl optionally substituted with one or more groups selected from the group consisting of halogen and C_3-6-cycloalkyl; R⁸ is hydrogen, C1-4-alkyl, or C3-6-cycloalkyl; and R^8b is hydrogen, C1-4-alkyl, C1-4-haloalkyl, or C3-6-cycloalkyl. In another embodiment of the compound of Formula (IC) or compound of Formula (ID), the present invention provides a compound of Formula (IC) and Formula (ID), or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein: R¹ and R² are independently hydrogen; halogen; nitro; cyano; C_1-4-alkyl optionally substituted with one or more groups selected from the group consisting of halogen, -O-R^8b, -N(H)R⁸, -N(alkyl)R⁸, C3-6-cycloalkyl, piperidinyl, pyrrolidinyl, and morpholinyl, in which said C_3-6-cycloalkyl, piperidinyl, pyrrolidinyl, and morpholinyl may be further substituted with one or more groups selected from the group consisting of halogen, cyano, -O-R^8b, C1-4-alkyl, C1-4-haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; C3-6-cycloalkyl optionally substituted with one or more groups selected from the group consisting of halogen, cyano, -O-R^8b, C_1-4-alkyl, C_1-4- haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; piperidinyl, pyrrolidinyl, morpholinyl, or 6- azaspiro[2.5]octyl, each of which may be substituted with one or more groups selected from the group consisting of halogen, cyano, -O-R^8b, C_1-4-alkyl, -CH₂- OR^8b, C1-4-haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; pyrazolyl optionally substituted with one or more groups selected from the group consisting of halogen, cyano, C1- ₄-alkyl, -O-(C_1-4-alkyl), C_1-4-haloalkyl, -O-(C_1-4-haloalkyl), -N(alkyl)alkyl, - N(H)alkyl, and -NH2; C2-4 alkenyl; -OR^7b; or -N(R^7b)2; R^7b is hydrogen; C_3-6-cycloalkyl; or C_1-4-alkyl optionally substituted with one or more groups selected from the group consisting of halogen and C_3-6-cycloalkyl; R⁸ is hydrogen, C_1-4-alkyl, or C_3-6-cycloalkyl; and R^8b is hydrogen, C1-4-alkyl, C1-4-haloalkyl, or C3-6-cycloalkyl. In another embodiment of the compound of Formula (IC) or compound of Formula (ID), the present invention provides a compound of Formula (IC) and (ID), or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein: Y is CH; R¹ is C_1-4-alkyl; R² is C_3-6-cycloalkyl; heterocycle; heteroaryl; -OR^7b; or C_1-4-alkyl optionally substituted with one or more -O-R^8b; R^7b is C_3-6-cycloalkyl or C_1-4-alkyl; R^8b is hydrogen, C_1-4-alkyl, C_1-4-haloalkyl, or C_3-6-cycloalkyl. In another embodiment of the compound of Formula (IC) or compound of Formula (ID), the present invention provides a compound of Formula (IC) and (ID), or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein: Y is CH; R¹ is C1-4-alkyl; R² is C3-6-cycloalkyl; piperidinyl; pyrrolidinyl; morpholinyl; 6-azaspiro[2.5]octyl; pyrazolyl; -OR^7b; or C_1-4-alkyl optionally substituted with one or more -O-R^8b; R^7b is C3-6-cycloalkyl or C1-4-alkyl; R^8b is hydrogen, C1-4-alkyl, C1-4-haloalkyl, or C3-6-cycloalkyl. In another embodiment of the compound of Formula (IC) or compound of Formula (ID), the present invention provides a compound of Formula (IC) and (ID), or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein: Y is CH; R¹ is C3-6-cycloalkyl; heterocycle; heteroaryl; -OR^7b; or C1-4-alkyl optionally substituted with one or more -O-R^8b; R² is C1-4-alkyl; R^7b is C3-6-cycloalkyl or C1-4-alkyl; R^8b is hydrogen, C1-4-alkyl, C1-4-haloalkyl, or C3-6-cycloalkyl. In another embodiment of the compound of Formula (IC) or compound of Formula (ID), the present invention provides a compound of Formula (IC) and (ID), or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein: Y is CH; R¹ is C3-6-cycloalkyl; piperidinyl; pyrrolidinyl; morpholinyl; 6-azaspiro[2.5]octyl; pyrazolyl; -OR^7b; or C_1-4-alkyl optionally substituted with one or more -O-R^8b; R² is C_1-4-alkyl; R^7b is C3-6-cycloalkyl or C1-4-alkyl; R^8b is hydrogen, C1-4-alkyl, C1-4-haloalkyl, or C3-6-cycloalkyl. The particular compounds obtained from compound of Formula (I) without departing from the scope of the definitions given under compounds of Formula (I) and particular compounds emanating from Formulas (I), (IA), (IB), (IC) and (ID) are summarized herein below in Table 1 encompassing the entirety of the scope of compounds within compound of Formula (I). Table 1: List of compounds of Formula (I) with structures

The “or1” in chemical structures indicates one or the other wedged bonds are valid at the given stereocenter (pure but unknown). In another embodiment, the present invention provides the use of the compounds of Formula (I) or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof. Unless specifically indicated, the general Formula (I) shall encompass tautomers and all stereo, optical and geometrical isomers (e.g. enantiomers, diastereomers, E/Z isomers, etc.) and racemates thereof as well as mixtures in different proportions of the separate enantiomers, mixtures of diastereomers, or mixtures of any of the foregoing forms where such isomers and enantiomers exist, as well as salts, including pharmaceutically acceptable salts thereof and solvates thereof such as for instance hydrates including solvates and hydrates of the free compound or solvates and hydrates of a salt of the compound. In general, substantially pure stereoisomers can be obtained according to synthetic principles known to a person skilled in the field, e.g. by separation of corresponding mixtures, by using stereochemically pure starting materials and/or by stereoselective synthesis. It is known in art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis, e.g. starting from optically active starting materials and/or by using chiral reagents. The term “pharmaceutically acceptable salt” is taken to mean an active ingredient, which comprises a compound of the Formula (I) in the form of one of its salts, in particular if this salt form imparts improved pharmacokinetic properties on the active ingredient compared with the free form of the active ingredient or any other salt form of the active ingredient used earlier. The pharmaceutically acceptable salt form of the active ingredient can also provide this active ingredient for the first time with a desired pharmacokinetic property which it did not have earlier and can even have a positive influence on the pharmacodynamics of this active ingredient with respect to its therapeutic efficacy in the body. Compounds having basic amine groups can form pharmaceutically acceptable salts with pharmaceutically acceptable acid(s). Suitable pharmaceutically acceptable acid addition salts of the compounds described herein include salts of inorganic acids (such as hydrochloric, hydrobromic, phosphoric, nitric, and sulfuric acids) and of organic acids (such as, e.g., acetic, trifluoroacetic, benzenesulfonic, benzoic, methanesulfonic, and p- toluenesulfonic acids). Compounds with acidic groups such as carboxylic acids can form pharmaceutically acceptable salts with pharmaceutically acceptable base(s). Suitable pharmaceutically acceptable basic salts include ammonium salts, alkali metal salts (such as sodium and potassium salts) and alkaline earth metal salts (such as magnesium and calcium salts). The term “regioisomer” or “regioisomers” refers to the positional isomers, which is a category of structural isomers, wherein the position or the substituent changes position on the parent structure. Herein the term regioisomer without departing from the scope of compounds of Formula (I) inherently includes all regioisomers either as a pure regioisomer or mixture of two or more regioisomers thereof. Since the pharmaceutical activity of the regioisomers of the compounds of the present invention may differ, it may be desirable to use the regioisomers. In these cases, the regioisomers can be separated at any of the possible stage either as an intermediate or as an end product by the process well known to the person skilled in the art or even employed as such in the synthesis. The term “tautomer” or “tautomers” refers to the compounds of Formula (I) of the present invention wherein any hydrogen atom is replaced by a hydroxyl group on a carbon with a double bond. The present invention includes all possible tautomeric forms. The term “prodrugs” refers to a compound having a group that can be converted into an amino group, a hydroxyl group, a carboxyl group, or the like, by solvolysis or under a physiological condition. Examples of the group for forming a prodrug include groups as described in Prog. Med., 5, 2157-2161 (1985). The present invention further provides a pharmaceutical composition comprising at least one compound according to Formula (I), or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, and a pharmaceutically acceptable excipient or carrier. "Pharmaceutically acceptable excipient" and "pharmaceutically acceptable carrier" refer to a substance that aids the formulation and/or administration of an active agent to and/or absorption by a subject and can be included in the compositions of the present disclosure without causing a significant adverse toxicological effect on the subject. Non-limiting examples of pharmaceutically acceptable carriers and/or diluents include water, NaCl, normal saline solutions, lactated Ringer's, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavors, salt solutions (such as Ringer's solution), alcohols, oils, gelatins, carbohydrates such as lactose, amylose or starch, fatty acid esters, hydroxymethylcellulose, polyvinyl pyrrolidine, and colors, and the like. Such preparations can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, and/or aromatic substances and the like that do not deleteriously react with or interfere with the activity of the compounds provided herein. One of ordinary skill in the art will recognize that other pharmaceutical excipients are suitable for use with disclosed compounds. Disclosed herein are methods of treating a disease modulated at least in part by PKMYT1 in a subject in need thereof, comprising administering to the subject a therapeutically affective amount of a compound, or a pharmaceutically acceptable salt thereof, disclosed herein. A "subject" is a mammal, preferably a human, but can also be an animal in need of veterinary treatment, e.g., companion animals (e.g., dogs, cats, and the like), farm animals (e.g., cows, sheep, pigs, horses, and the like) and laboratory animals (e.g., rats, mice, guinea pigs, and the like). Disclosed herein is a method of treating in a subject in need thereof, the method comprising administering to the subject a therapeutically affective amount of a compound, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, cancer depends on the activity of PKMYT1. In some embodiments, cancer overexpresses CCNE1. In some embodiments cancers includes, but not limited to, which have a high incidence of CCNE1 overexpression include e.g., breast cancer, endometrial cancer, esophageal cancer, lung cancer, ovarian cancer, stomach cancer, and uterine cancer. In some embodiments, the cancer has an inactivating mutation includes, but not limited to, FBXW7 and PPP2R1A genes. In some embodiments cancers which have a deficiency in FBXW7 and PPP2R1A include, e.g., breast cancer, colorectal cancer, esophageal cancer, lung cancer, and uterine cancer. In some embodiments, cancer is a solid tumor. In some embodiments, the cancer includes, but not limited to, breast cancer, colorectal cancer, endometrial cancer, esophageal cancer, glioblastoma, hepatocellular carcinoma, lung cancer, neuroblastoma, ovarian cancer, prostate cancer, stomach cancer, or uterine cancer. Pharmaceutical formulations can be adapted for administration via any desired suitable method, for example by oral (including buccal or sublingual), rectal, nasal, topical (including buccal, sublingual or transdermal), vaginal or parenteral (including subcutaneous, intramuscular, intravenous or intradermal) methods. Such formulations can be prepared using all processes known in the pharmaceutical art by, for example, combining the active ingredient with the excipient(s) or adjuvant(s). Pharmaceutical formulations adapted for oral administration can be administered as separate units, such as, for example, capsules or tablets; powders or granules; solutions or suspensions in aqueous or non-aqueous liquids; edible foams or foam foods; or oil-in-water liquid emulsions or water-in-oil liquid emulsions. For example, in the case of oral administration as tablet or capsule, the active- ingredient component can be combined with an oral, non-toxic and pharmaceutically acceptable inert excipient, such as, for example, ethanol, glycerol, water and the like. Powders are prepared by comminuting the compound to a suitable fine size and mixing it with a pharmaceutical excipient comminuted in a similar manner, such as, for example, an edible carbohydrate, such as, for example, starch or mannitol. A flavor, preservative, dispersant and dye may likewise be present. Capsules are produced by preparing a powder mixture as described above and filling shaped gelatine shells therewith. Glidants and lubricants, such as, for example, highly disperse silicic acid, talc, magnesium stearate, calcium stearate or polyethylene glycol in solid form can be added to the powder mixture before the filling operation. A disintegrant or solubilizer, such as, for example, agar-agar, calcium carbonate or sodium carbonate, may likewise be added in order to improve the availability of the medicament after the capsule has been taken. In addition, if desired or necessary, suitable binders, lubricants and disintegrants as well as dyes can likewise be incorporated into the mixture. Suitable binders include starch, gelatine, natural sugars, such as, for example, glucose or beta-lactose, sweeteners made from maize, natural and synthetic rubber, such as, for example, acacia, tragacanth or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes, and the like. The lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like. The disintegrants include, without being restricted thereto, starch, methylcellulose, agar, bentonite, xanthan gum and the like. The tablets are formulated by, for example, preparing a powder mixture, granulating or dry pressing the mixture, adding a lubricant and a disintegrant and pressing the entire mixture to give tablets. A powder mixture is prepared by mixing the compound comminuted in a suitable manner with a diluent or a base, as described above, and optionally with a binder, such as, for example, carboxymethylcellulose, an alginate, gelatine or polyvinyl-pyrrolidone, a dissolution retardant, such as, for example, paraffin, an absorption accelerator, such as, for example, a quaternary salt, and/or an absorbant, such as, for example, bentonite, kaolin or dicalcium phosphate. The powder mixture can be granulated by wetting it with a binder, such as, for example, syrup, starch paste, acadia mucilage or solutions of cellulose or polymer materials and pressing it through a sieve. As an alternative to granulation, the powder mixture can be run through a tableting machine, giving lumps of non-uniform shape which are broken up to form granules. The granules can be lubricated by addition of stearic acid, a stearate salt, talc or mineral oil in order to prevent sticking to the tablet casting moulds. The lubricated mixture is then pressed to give tablets. The active ingredients can also be combined with a free-flowing inert excipient and then pressed directly to give tablets without carrying out the granulation or dry-pressing steps. A transparent or opaque protective layer consisting of a shellac sealing layer, a layer of sugar or polymer material and a gloss layer of wax may be present. Dyes can be added to these coatings in order to be able to differentiate between different dosage units. Oral liquids, such as, for example, solution, syrups and elixirs, can be prepared in the form of dosage units so that a given quantity comprises a pre-specified amount of the compounds. Syrups can be prepared by dissolving the compounds in an aqueous solution with a suitable flavour, while elixirs are prepared using a non- toxic alcoholic vehicle. Suspension can be formulated by dispersion of the compounds in a non-toxic vehicle. Solubilisers and emulsifiers, such as, for example, ethoxylated isostearyl alcohols and polyoxyethylene sorbitol ethers, preservatives, flavour additives, such as, for example, peppermint oil or natural sweeteners or saccharin, or other artificial sweeteners and the like, can likewise be added. The dosage unit formulations for oral administration can, if desired, be encapsulated in microcapsules. The formulation can also be prepared in such a way that the release is extended or retarded, such as, for example, by coating or embedding particulate material in polymers, wax and the like. The formulations can be in the form of liposome delivery systems, such as, for example, small unilamellar vesicles, large unilamellar vesicles and multilamellar vesicles. Liposomes can be formed from suitable lipids or phospholipids or both, such as, for example, cholesterol, stearylamine or phosphatidylcholines or the like. Pharmaceutical formulations adapted for transdermal administration can be administered as independent plasters for extended, close contact with the epidermis of the recipient. Thus, for example, the active ingredient can be delivered from the plaster by iontophoresis, as described in general terms in Pharmaceutical Research, 3(6), 318 (1986). Pharmaceutical compounds adapted for topical administration can be formulated as ointments, creams, suspensions, lotions, powders, solutions, pastes, gels, sprays, aerosols or oils. Pharmaceutical formulations adapted for topical application to the eye include eye drops, in which the active ingredient is dissolved or suspended in a suitable carrier, in particular an aqueous solvent. Pharmaceutical formulations adapted for topical application in the mouth encompass lozenges, pastilles and mouthwashes. Pharmaceutical formulations adapted for rectal administration can be administered in the form of suppositories or enemas. Pharmaceutical formulations adapted for nasal administration in which the carrier substance is a solid comprise a coarse powder having a particle size, for example, in the range 20-500 microns, which is administered in the manner in which snuff is taken, i.e. by rapid inhalation via the nasal passages from a container containing the powder held close to the nose. Suitable formulations for administration as nasal spray or nose drops with a liquid as carrier substance encompass active-ingredient solutions in water or oil. Pharmaceutical formulations adapted for administration by inhalation encompass finely particulate dusts or mists, which can be generated by various types of pressurized dispensers with aerosols, nebulizers or inhalers. Pharmaceutical formulations adapted for vaginal administration can be administered as pessaries, tampons, creams, gels, pastes, foams or spray formulations. Pharmaceutical formulations adapted for parenteral administration include aqueous and non- aqueous sterile injection solutions comprising antioxidants, buffers, bacteriostatics and solutes, by means of which the formulation is rendered isotonic with the blood of the recipient to be treated; and aqueous and non-aqueous sterile suspensions, which may comprise suspension media and thickeners. The formulations can be administered in single-dose or multidose containers, for example sealed ampoules and vials, and stored in freeze-dried (lyophilized) state, so that only the addition of the sterile carrier liquid, for example water for injection purposes, immediately before use is necessary. Injection solutions and suspensions prepared in accordance with the recipe can be prepared from sterile powders, granules and tablets. In addition to the above particularly mentioned constituents, the formulations may also comprise other agents usual in the art with respect to the particular type of formulation; thus, for example, formulations which are suitable for oral administration may comprise flavors. A therapeutically effective amount of a compound of the Formula (I) and of the other active ingredients depends on a number of factors, including, for example, the age and weight of the animal, the precise disease condition which requires treatment, and its severity, the nature of the formulation and the method of administration, and is ultimately determined by the treating doctor or vet. However, an effective amount of a compound is generally in the range from 0.1 to 100 mg/kg of body weight of the recipient (mammal) per day and particularly typically in the range from 1 to 10 mg/kg of body weight per day. Thus, the actual amount per day for an adult mammal weighing 70 kg is usually between 70 and 700 mg, where this amount can be administered as an individual dose per day or usually in a series of part-doses (such as, for example, two, three, four, five or six) per day, so that the total daily dose is the same. An effective amount of a salt or solvate or of a physiologically functional derivative thereof can be determined as the fraction of the effective amount of the compound per se. In a further aspect, the present invention relates to a process for preparing novel compounds of Formula (I). In further aspect, the present invention provides a process of preparing novel compounds of Formula (I). The novel heteroaryl compounds of Formula (I) may be prepared using the following general method and procedures. It will be appreciated that where typical or preferred experimental conditions (i.e. reaction temperatures, time, moles of reagents, solvents etc.) are given, other experimental conditions can also be used unless otherwise stated. Optimum reaction conditions may vary with the particular reactants or solvents used, but such conditions can be determined by the person skilled in the art, using routine optimization procedures. Moreover, by utilizing the procedures described in detail, one of the ordinary skills in art can prepare additional compounds of the present invention claimed herein. All temperatures are in degrees Celsius (°C) unless otherwise noted. The processes described herein may enable the synthesis of the compounds of the present invention. However, these may not be the only means by which the compounds described in the invention may be synthesized. Further, the various synthetic steps described herein may be performed in alternate sequences to furnish the desired compounds. In one embodiment the present invention provides a process for preparing the compounds of Formula (I), particularly Formula (IA) and (IB) depicted in the Schemes given hereunder. One skilled-in-the-art will recognize that any of the Schemes can be adapted to produce the compounds of Formula (I) and pharmaceutically accepted salts of compounds of Formula (I) according to the present invention. All symbols/variables are as defined hereunder unless otherwise stated. In another embodiment, the present invention provides a general process for preparing the compounds of the Formula (IA) and (IB) obtained using compound (a) as a starting material as seen in scheme I.

Scheme 1 In another embodiment, the present invention provides a process for preparing compound of Formula (IA) comprising the steps of: Step i): The starting compound (a) is prepared by the method disclosed in prior-art and is treated with compound (d) by using the methods known in the art for Buchwald–Hartwig amination reaction. The ring A in compound (d) is preferably phenyl. The base used in the process is selected from a group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, magnesium carbonate, wherein the preferred base is caesium carbonate. The catalyst used in the process is selected from a group comprising Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2dppf .CH2Cl2), Palladium(II) acetate ([Pd(OAc)2]n), tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4) or tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3), wherein the preferred catalyst is Tris(dibenzylideneacetone)dipalladium(0). The solvent used in the reaction is selected from the group comprising diethyl ether, tetrahydrofuran, dimethoxy ethane, dimethoxy methane, dibutyl ether, diisopropyl ether, wherein the preferred solvent is 1,2dimethoxy ethane. The suitable base and solvent are mixed with the starting compounds (a) and (d). The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Tris(dibenzylideneacetone)dipalladium(0) at temperature ranging from 100 to 150⁰C to obtain compound (b). Step ii): The resulting compound (b) as obtained in step i) is further treated with nitrile selected from a group comprising malononitrile, propionitrile, ethanenitrile, benzonitrile and the like, wherein malononitrile is preferred. The said reaction is performed in presence of suitable base selected from group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, wherein the preferred base is sodium tertiary butoxide or sodium hydride. The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Bis(diphenylphosphino)ferrocene]dichloropalladium(II). The reaction is carried out in presence of suitable solvent selected from group comprising 1,2-dimethoxy ethane, toluene, tetrahydrofuran, diethyl ether or chlorinated solvent thereof at a temperature ranging from 100 to 150⁰C to obtain compound (c), wherein ring A is phenyl. Step iii): The resulting compound (c) as obtained in step ii), is further treated with suitable reagents selected from a group comprising formamide, ethyl carbonate, or guanidine hydrochloride to form heteroaryls or heterocycles compound. Step iv): The compound of step iii) is further subjected to deprotection of protecting group using methods known in the art to obtain compound of Formula (IA). In the present embodiment, scheme I provides compound of Formula (IA), wherein: ring A is phenyl; X is N, Y is -CH-; R¹ and R² are methyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-8 membered heterocycle, or substituted- or unsubstituted- 5-6 membered heteroaryl. In another embodiment, the present invention provides a process for preparing compound of Formula (IB) comprising the steps of: Step i): The starting compound (a) is prepared by the method disclosed in prior-art and is treated with compound (d) by using the methods known in the art for Buchwald–Hartwig amination reaction. The ring A in compound (d) is preferably phenyl. The base used in the process is selected from a group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, magnesium carbonate, wherein the preferred base is caesium carbonate. The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Tris(dibenzylideneacetone)dipalladium(0). The solvent used in the reaction is selected from the group comprising diethyl ether, tetrahydrofuran, dimethoxy ethane, dimethoxy methane, dibutyl ether, diisopropyl ether, wherein the preferred solvent is 1,2-dimethoxy ethane. The suitable base and solvent is mixed with the starting compounds (a) and compound (d) in presence of catalyst Tris(dibenzylideneacetone)dipalladium(0) at temperature ranging from 100 to 150⁰C to obtain compound (b). Step ii): The resulting compound (b) as obtained in step i) is further treated with nitrile selected from a group comprising malononitrile, propionitrile, ethanenitrile, benzonitrile and the like, wherein malononitrile is preferred. The said step is carried in presence of suitable base selected from group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, wherein the preferred base is sodium tertiary butoxide or sodium hydride. The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Bis(diphenylphosphino)ferrocene]dichloropalladium(II). The reaction is carried out in presence of suitable solvent selected from group comprising 1,2-dimethoxy ethane, toluene, tetrahydrofuran, diethyl ether or chlorinated solvent thereof at a temperature ranging from 100 to 150⁰C to obtain compound (c). Step iii): The resulting compound (c) as obtained in step ii) is treated with reagents selected from group comprising sulfuric acid, hydrogen peroxide, hydrochloric acid, acetic acid, sodium bicarbonate, potassium bicarbonate, calcium bicarbonate, wherein the preferred reagent is sulfuric acid or hydrogen peroxide. The said reagents are provided in the presence of suitable base selected from lithium hydroxide, potassium hydroxide, sodium hydroxide, magnesium hydroxide, wherein the preferred base is lithium hydroxide. Step iv): The compound (c) is further subjected to deprotection of protecting group using methods known in the art to give compounds of Formula (IB). In the present embodiment, scheme I provides compound of Formula (IB), wherein: ring A is phenyl; X is N, Y is -CH-; R¹ and R² are methyl; R³ is -C(=O)N(R^7b)2, and R⁴ is -N(R^7b)2; where R^7b is hydrogen. In yet another embodiment, the present invention provides a process of preparing compound of the Formula (IA) from the compounds (e), (h) and (j) as seen in scheme 2.

Scheme 2 In another embodiment the present invention provides a process for preparing compound of Formula (IA) comprising the steps of: Step i): A starting compound (e), wherein R¹ group is methyl, is prepared by the method disclosed in the prior art by treating with boronic acid selected from a group comprising phenylboronic acid, 4-methylphenylboronic acid, 4- fluorophenylboronic acid, 3-methylphenylboronic acid, 4-carboxyphenylboronic acid, 3-carboxyphenylboronic acid, 4-acetamidophenylboronic acid and the likes by using the methods known in the art for Suzuki coupling followed by reduction of the nitro group to obtain compound (f). Step ii): The compound (f) obtained in step i) is treated with bromine or N- bromosuccinimide to obtain compound (g), wherein R¹ is methyl and R² is alkyl or cycloalkyl. The compound (g) is further treated with sodium nitrite for diazotization followed by treatment with phosphoryl bromide (POBr₃) to obtain compound (a), wherein R¹ is methyl, R² is alkyl, cycloalkyl, heterocycle, heteroaryl or -OR^7b, wherein R^7b is alkyl or cycloalkyl. Step iii): As provided in general scheme, the compound (a) obtained by step ii) is used as a starting material which is treated with compound (d) by using the methods known in the art for Buchwald–Hartwig amination reaction. The ring A in compound (d) is preferably phenyl. The base used in the process is selected from a group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, magnesium carbonate, wherein the preferred base is caesium carbonate. The catalyst used in the process is selected from group comprising Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Tris(dibenzylideneacetone)dipalladium(0). The solvent used in the reaction is selected from the group comprising diethyl ether, tetrahydrofuran, dimethoxy ethane, dimethoxy methane, dibutyl ether, diisopropyl ether, wherein the preferred solvent is 1,2-dimethoxy ethane. The suitable base and solvent are mixed with the compound (a) and compound (d). The reaction is carried out in the presence of a suitable catalyst at desired temperature ranging from 100 to 150⁰C to obtain compound (b), wherein ring A is phenyl. Step iv): The resulting compound (b) as obtained in step iii) is further treated with malononitrile in presence of suitable base selected from group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, wherein the preferred base is sodium tertiary butoxide or sodium hydride. The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Bis(diphenylphosphino)ferrocene]dichloropalladium(II). The reaction is carried out in presence of suitable solvent selected from group comprising 1,2-dimethoxy ethane, toluene, tetrahydrofuran, diethyl ether or chlorinated solvent thereof at a temperature ranging from 100 to 150⁰C to obtain compound (c), wherein ring A is phenyl, R¹ is methyl, R² is cycloalkyl or heterocycle or heteroaryl or -OR^7b, wherein R^7b is alkyl or cycloalkyl. Step v): The resulting compound (c) as obtained in step iv), is further treated with suitable reagents selected from a group comprising formamide, ethyl carbonate, or guanidine hydrochloride to form heteroaryls i.e., compound (m). Step vi): The resulting compound (m) is subjected to deprotection of protecting group using the methods known in the art to obtain the compound of Formula (IA). In another embodiment the present invention provides a process for preparing compound of Formula (IA) comprising the steps of: Step i): The starting compound (h), wherein R¹ is methyl group, is prepared by the method disclosed in prior-art, and treated with dihalides selected from group comprising 1,2dichloroethane, 1,2dichlorobutane, 1,2dibromoethane, 1, 2- dibromobutane and the likes, in presence of a suitable base selected from group comprising sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, calcium carbonate, sodium carbonate, potassium carbonate to obtain compound (i), wherein R¹ is methyl and R² is heterocycle. Step ii): The compound (i) obtained in previous step i) is further treated with N- bromosuccinimide or bromine or the likes to obtain compound (a), wherein R¹ is methyl, R² is alkyl, cycloalkyl, heterocycle, heteroaryl or -OR^7b, wherein R^7b is alkyl or cycloalkyl. Step iii): As provided in general scheme, the compound (a) is used as a starting material and treated with compound (d) by using the methods known in the art for Buchwald–Hartwig amination reaction. The ring A in compound (d) is preferably phenyl. The base used in the process is selected from a group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, magnesium carbonate, wherein the preferred base is caesium carbonate. The catalyst used in the process is selected from group comprising Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Tris(dibenzylideneacetone)dipalladium(0). The solvent used in the reaction is selected from the group comprising diethyl ether, tetrahydrofuran, dimethoxy ethane, dimethoxy methane, dibutyl ether, diisopropyl ether, wherein the preferred solvent is 1,2-dimethoxy ethane. The suitable base and solvent are mixed with the compound (a) and compound (d). The reaction is carried out in the presence of suitable catalyst, wherein the temperature is ranging from 100 to 150⁰C to obtain compound (b), wherein ring A is phenyl. Step iv): The resulting compound (b) as obtained in step iii) is further treated with malononitrile in presence of suitable base selected from group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, wherein the preferred base is sodium tertiary butoxide or sodium hydride. The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Bis(diphenylphosphino)ferrocene]dichloropalladium(II). The reaction is carried out in presence of suitable solvent selected from group comprising 1,2-dimethoxy ethane, toluene, tetrahydrofuran, diethyl ether or chlorinated solvent thereof at a temperature ranging from 100 to 150⁰C to obtain compound (c), wherein ring A is phenyl, R¹ is methyl, R² is cycloalkyl or heterocycle or heteroaryl or -OR^7b, wherein R^7b is alkyl or cycloalkyl. Step v): The resulting compound (c) as obtained in step iv), is further treated with suitable reagents selected from the group comprising formamide, ethyl carbonate, or guanidine hydrochloride to form heteroaryls i.e., compound (m). Step vi): The resulting compound (m) is subjected to deprotection of protecting group using the methods known in the art to obtain compound of Formula (IA). In another embodiment the present invention provides a process for preparing compound of Formula (IA) comprising the steps of: Step i): The starting compound (j) is prepared by the method disclosed in prior-art, wherein R¹ is methyl group. The compound (j) is treated with N-bromosuccinimide or bromine to obtain compound (k). The compound (k) is further treated with sodium nitrite for diazotization followed by treatment with phosphoryl bromide (POBr₃) to obtain compound (l), wherein R¹ is methyl. Step ii): The compound (l) obtained in previous step i) are treated with heterocycles to obtain compound (a), wherein R¹ is methyl, R² is alkyl, cycloalkyl, heterocycle, heteroaryl or -OR^7b, wherein R^7b is alkyl or cycloalkyl. Step iii): As provided in general scheme, the compound (a) prepared by step ii) as starting material is treated with compound (d) by using the methods known in the art for Buchwald–Hartwig amination reaction. The ring A in compound (d) is preferably phenyl. The base used in the process is selected from a group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, magnesium carbonate, wherein the preferred base is caesium carbonate. The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Tris(dibenzylideneacetone)dipalladium(0). The solvent used in the reaction is selected from the group comprising diethyl ether, tetrahydrofuran, dimethoxy ethane, dimethoxy methane, dibutyl ether, diisopropyl ether, wherein the preferred solvent is 1,2dimethoxy ethane. The suitable base and solvent is mixed with the compound (a) and compound (d) in presence of catalyst Tris(dibenzylideneacetone)dipalladium(0) at temperature ranging from 100 to 150⁰C to obtain compound (b), wherein ring A is phenyl. Step iv): The resulting compound (b) as obtained in step iii) is further treated with malononitrile in presence of suitable base selected from a group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, wherein the preferred base is sodium tertiary butoxide or sodium hydride. The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Bis(diphenylphosphino)ferrocene]dichloropalladium(II). The reaction is carried out in presence of suitable solvent selected from group comprising 1,2-dimethoxy ethane, toluene, tetrahydrofuran, diethyl ether or chlorinated solvent thereof at a temperature ranging from 100 to 150⁰C to obtain compound (c), wherein ring A is phenyl, R¹ is methyl, R² is cycloalkyl or heterocycle or heteroaryl or -OR^7b, wherein R^7b is alkyl or cycloalkyl. Step v): The resulting compound (c) as obtained in step iv), is further treated with suitable reagents selected from the group comprising formamide, ethyl carbonate, or guanidine hydrochloride to form heteroaryls i.e., compound (m). Step vi): The compound (m) is subjected to deprotection of protecting group using the methods known in the art to obtain compound of Formula (IA). In the present embodiment, scheme 2 provides compound of Formula (IA), wherein: ring A is phenyl; X is N, Y is -CH-; R¹ is methyl; R² is cycloalkyl or heterocycle or heteroaryl or OR^7b, wherein R^7b alkyl or cycloalkyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-6 membered heteroaryl. In yet another embodiment, the present invention provides a process of preparing compound of the Formula (IA) from scheme 3:

Scheme 3 Scheme 3 shows a method of preparation of the compound of the Formula (IA) from compound (q) or (t). In another embodiment, the present invention provides a process for preparing compound of Formula (IA) comprising the steps of: Step i): The starting compound (q) is prepared by the method disclosed in prior art and is treated with boronic acid selected from a group comprising phenylboronic acid, 4-methylphenylboronic acid, 4-fluorophenylboronic acid, 3- methylphenylboronic acid, 4-carboxyphenylboronic acid, 3-carboxyphenylboronic acid, 4-acetamidophenylboronic acid and the likes by using the methods known in the art for Suzuki coupling followed by reduction of the nitro group to obtain compound (r). Step ii): The compound (r) obtained in step i) is treated with bromine or N- bromosuccinimide or likes to obtain the compound (s), wherein R² is methyl, R¹ is alkyl, cycloalkyl, heterocycle, -OR^7b, wherein R^7b is alkyl or cycloalkyl. Step iii): The compound (s) obtained in step ii) is further treated with sodium nitrite for diazotization in presence of mineral acids selected from nitric acid, phosphoric acid, boric acid, hydrochloric acid, sulfuric acid, hydrofluoric acid, wherein the preferred acid is nitric acid. This reaction is followed by treatment with reactants selected from the group comprising phosphoryl bromide (POBr₃), 1-bromopropane, 2-bromopropane, bromomethane, boron tribromide, wherein phosphoryl bromide is preferred to obtain compound (a), wherein R² is methyl, R¹ is alkyl, cycloalkyl, heterocycle, -OR^7b, wherein R^7b is alkyl or cycloalkyl. Step iv): As provided in general scheme, compound (a) obtained in step iii) is used as a starting material and treated with compound (d) by using the methods known in the art for Buchwald–Hartwig amination reaction. The base used in the process is selected from a group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, magnesium carbonate, wherein the preferred base is caesium carbonate. The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Tris(dibenzylideneacetone)dipalladium(0). The solvent used in the reaction is selected from the group comprising diethyl ether, tetrahydrofuran, dimethoxy ethane, dimethoxy methane, dibutyl ether, diisopropyl ether, wherein the preferred solvent is 1,2-dimethoxy ethane. The suitable base and solvent are mixed with the compound (v) and compound (d) in presence of suitable catalyst at temperature ranging from 100 to 150⁰C to obtain the compound (b), wherein ring A is phenyl. Step v): The resulting compound (b) obtained in the previous step iv) is treated with malononitrile in presence of suitable base selected from group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, wherein the preferred base is sodium tertiary butoxide or sodium hydride. The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Bis(diphenylphosphino)ferrocene]dichloropalladium(II). The reaction is carried out in presence of suitable solvent selected from group comprising 1,2-dimethoxy ethane, toluene, tetrahydrofuran, diethyl ether or chlorinated solvent at 100 to 150⁰C to obtain compound (c), wherein ring A is phenyl, R² is methyl, R¹ is cycloalkyl or heterocycle or -OR^7b, wherein R^7b is alkyl or cycloalkyl. Step vi): The compound (c) obtained in previous step v), is treated with suitable reagents selected from the group comprising formamide, ethyl carbonate, or guanidine hydrochloride to form heteroaryls i.e., compound (m). Step vii): The compound (m) is subjected to deprotection of protecting group using the methods known in the art to obtain compound of Formula (IA). In another embodiment, the present invention provides a process for preparing compound of Formula (IA) comprising the steps of: Step i): The starting compound (t) is prepared by the method disclosed in prior-art and is treated with dihalides selected from group comprising 1,2-dichloroethane, 1,2-dichlorobutane, 1,2-dibromoethane, 1, 2-dibromobutane and the likes, in presence of a suitable base selected from group comprising sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, calcium carbonate, sodium carbonate, potassium carbonate to obtain compound (u), wherein R² is methyl, R¹ is heterocycle. Step (ii): The compound (u) is further treated with N-bromosuccinimide or bromine or likes to obtain compound (a), wherein R² is methyl, R¹ is alkyl, cycloalkyl, heterocycle, -OR^7b, wherein R^7b is alkyl or cycloalkyl. Step iii): As provided in general scheme, the compound (a) is used as starting material and treated with compound (d) by using the methods known in the art for Buchwald–Hartwig amination reaction. The base used in the process is selected from a group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, magnesium carbonate, wherein the preferred base is caesium carbonate. The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Tris(dibenzylideneacetone)dipalladium(0). The solvent used in the reaction is selected from the group comprising diethyl ether, tetrahydrofuran, dimethoxy ethane, dimethoxy methane, dibutyl ether, diisopropyl ether, wherein the preferred solvent is 1,2-dimethoxy ethane. The suitable base and solvent are mixed with the compound (a) and compound (d) in presence of suitable catalyst at temperature ranging from 100 to 150⁰C to obtain the compound (b), wherein ring A is phenyl. Step iv): The compound (b) obtained in the previous step iii) is treated with malononitrile in presence of suitable base selected from group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, wherein the preferred base is sodium tertiary butoxide or sodium hydride. The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Bis(diphenylphosphino)ferrocene]dichloropalladium(II). The reaction is carried out in presence of suitable solvent selected from group comprising 1,2-dimethoxy ethane, toluene, tetrahydrofuran, diethyl ether or chlorinated solvent at temperature 100 to 150⁰C to obtain compound (c), wherein ring A is phenyl, R² is methyl, R¹ is cycloalkyl or heterocycle or -OR^7b, wherein R^7b is alkyl or cycloalkyl. Step v): The compound (c) obtained in previous step iv), is treated with suitable reagents selected from the group comprising formamide, ethyl carbonate, or guanidine hydrochloride to form heteroaryls i.e., compound (m). Step vi): The compound (m) is subjected to deprotection of protecting group using the methods known in the art to obtain compound of Formula (IA). In the present embodiment, scheme 3 provides compound of Formula (IA), wherein: ring A is phenyl; X is N, Y is -CH-; R¹ is cycloalkyl or heterocycle or OR^7b, wherein R^7b alkyl or cycloalkyl; R² is methyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-6 membered heteroaryl. In yet another embodiment, the present invention provides a process of preparing compound of the Formula (IA) from scheme 4:

Scheme 4 shows a method of preparation of the compound of the Formula (IA) from compound (v) or (w). In another embodiment, the present invention provides a process for preparing compound of Formula (IA) comprising the steps of: Step i): Compound (v) is prepared by the method disclosed in prior art (WO2008085119) and is treated with Phosphoryl bromide to obtain compound (w). The ethyl ester of the compound (w) is converted to Weinreb amide or compound (x) by the methods known in the art. Step ii): The resulting compound (x) as obtained in the previous step i) is treated with reagent selected from a group comprising methyl magnesium bromide, ethyl magnesium bromide, isopropyl magnesium bromide, allyl magnesium bromide or the likes, wherein the preferred reagent is methyl magnesium bromide to obtain the compound (y). Step iii): The resulting compound (y) as obtained in step ii) is further reduced to obtain corresponding compound (z) (an alcohol) by the methods known in the art. Step iv): The compound (z) as obtained in step iii) is alkylated using alkyl halides selected from a group comprising bromoethane, bromomethane, 1-chloropropane, 2-chloropropane, iso propyl bromide, tert-butyl bromide and likes and using base selected from a group comprising potassium carbonate, cesium carbonate, sodium carbonate, magnesium carbonate, sodium hydride, sodium tert-butoxide and the likes to obtain compound (a), wherein R¹ is methyl, R² is substituted alkyl, wherein substituent is -OR^8b. . Step v): As provided in general scheme, the compound (a) obtained in step iv) is used as a starting material which is treated with compound (d) by using the methods known in the art for Buchwald–Hartwig amination reaction. The ring A in compound (d) is preferably phenyl. The base used in the process is selected from a group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, magnesium carbonate, wherein the preferred base is caesium carbonate. The catalyst used in the process is selected from group comprising Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Tris(dibenzylideneacetone)dipalladium(0). The solvent used in the reaction is selected from the group comprising diethyl ether, tetrahydrofuran, dimethoxy ethane, dimethoxy methane, dibutyl ether, diisopropyl ether, wherein the preferred solvent is 1,2-dimethoxy ethane. The suitable base and solvent are mixed with the compound (a) and compound (d). The reaction is carried out in the presence of a suitable catalyst at desired temperature ranging from 100 to 150⁰C to obtain compound (b), wherein ring A is phenyl. Step vi): The resulting compound (b) as obtained in step v) is further treated with malononitrile in presence of suitable base selected from group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, wherein the preferred base is sodium tertiary butoxide or sodium hydride. The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Bis(diphenylphosphino)ferrocene]dichloropalladium(II). The reaction is carried out in presence of suitable solvent selected from group comprising 1,2-dimethoxy ethane, toluene, tetrahydrofuran, diethyl ether or chlorinated solvent thereof at a temperature ranging from 100 to 150⁰C to obtain compound (c), wherein ring A is phenyl, R¹ is methyl, R² is substituted alkyl, wherein substituent is -OR^8b. Step vii): The resulting compound (c) as obtained in step vi), is further treated with suitable reagents selected from a group comprising formamide, ethyl carbonate, or guanidine hydrochloride to form heteroaryls i.e., compound (m). Step viii): The resulting compound (m) is subjected to deprotection of protecting group using the methods known in the art to obtain the compound of Formula (IA). In another embodiment, the present invention provides a process for preparing compound of Formula (IA) comprising the steps of: Step i): The compound (w) is reduced to obtain the compound (α). Compounds (α) is further alkylated using alkyl halides selected from a group comprising bromoethane, bromomethane, 1-chloropropane, 2-chloropropane, iso propyl bromide, tert-butyl bromide and likes and by using base selected from group comprising potassium carbonate, Cesium carbonate, sodium carbonate, magnesium carbonate, sodium hydride, sodium tert-butoxide and the likes to obtain the compound (a), wherein R¹ is methyl, R² is substituted alkyl, wherein substituent is -OR^8b. Step ii): As provided in the scheme, the compound (a) obtained in step i) is used as a starting material which is treated with compound (d) by using the methods known in the art for Buchwald–Hartwig amination reaction. The ring A in compound (d) is preferably phenyl. The base used in the process is selected from a group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, magnesium carbonate, wherein the preferred base is caesium carbonate. The catalyst used in the process is selected from group comprising Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Tris(dibenzylideneacetone)dipalladium(0). The solvent used in the reaction is selected from the group comprising diethyl ether, ethyl acetate, tetrahydrofuran, dimethoxy ethane, dimethoxy methane, dibutyl ether, diisopropyl ether, wherein the preferred solvent is 1,2-dimethoxy ethane. The suitable base and solvent are mixed with the compound (a) and compound (d). The reaction is carried out in presence of a suitable catalyst and desired temperature ranging from 100 to 150⁰C to obtain compound (b), wherein ring A is phenyl. Step iii): The resulting compound (b) as obtained in step ii) is further treated with malononitrile in presence of suitable base selected from group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, wherein the preferred base is sodium tertiary butoxide or sodium hydride. The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Bis(diphenylphosphino)ferrocene]dichloropalladium(II). The reaction is carried out in presence of suitable solvent selected from group comprising 1,2-dimethoxy ethane, toluene, tetrahydrofuran, diethyl ether or chlorinated solvent thereof at a temperature ranging from 100 to 150⁰C to obtain compound (c), wherein ring A is phenyl, R¹ is methyl, R² is substituted alkyl, wherein substituent is -OR^8b. Step iv): The resulting compound (c) as obtained in step iii), is further treated with suitable reagents selected from a group comprising formamide, ethyl carbonate, or guanidine hydrochloride to form heteroaryls i.e., compound (m). Step v): The resulting compound (m) is subjected to deprotection of protecting group using the methods known in the art to obtain the compound of Formula (IA). In the present embodiment, scheme 4 provides compound of Formula (IA), wherein: ring A is phenyl; X is N, Y is -CH-; R¹ is methyl; R² is substituted alkyl, wherein substituent is -OR^8b; R^8b is selected from hydrogen, alkyl, haloalkyl, and cycloalkyl; R³ and R⁴ together can form h a substituted- or unsubstituted- 5-6 membered heteroaryl. In yet another embodiment, the present invention provides a process of preparing a compound of Formula (IC) and compound of Formula (ID). In general, the compound of Formula (IC) or compound of Formula (ID) or a pharmaceutically acceptable salt thereof may be prepared by removing a protective group of a compound of Formula (A1) or compound of Formula (A2) respectively:

wherein Pr¹ is protected hydroxy, Pr² is hydrogen or protected hydroxy, and R¹, R², R^5a, R^5b, and Y are the same as defined in the compound of Formula (IC) and compound of Formula (ID), or its salt. Suitable salts of the compound of Formulas (A1) and (A2) can be referred to as the salts as exemplified for the compound of Formula (I). A suitable protective group of the protected hydroxy of Pr¹ and Pr² is methyl or 4- methoxybenzyl, which can be removed by a conventional method and condition known in the art, for example by a similar condition to Examples 1 or 16 below. The compound of Formulas (A1) and (A2) may be prepared as shown in Scheme A as follows:

Scheme A wherein R¹, R², R^5a, R^5b, Y, Pr¹, and Pr² are the same as defined in the compound of Formulas (IC), (ID), (A1), and (A2). Step i): A compound of Formula (D) is prepared by reacting a compound of Formula (B) with a compound of Formula (C). The reaction is carried out in the same condition as mentioned in, for example, Step i) of Scheme I above i.e. The base used in the process is selected from a group comprising sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, magnesium carbonate, wherein the preferred base is caesium carbonate. The catalyst used in the process is selected from a group comprising Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2dppf .CH2Cl2), Palladium(II) acetate ([Pd(OAc)2]n), tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4) or tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3), wherein the preferred catalyst is Tris(dibenzylideneacetone)dipalladium(0). The solvent used in the reaction is selected from the group comprising diethyl ether, tetrahydrofuran, dimethoxy ethane, dimethoxy methane, dibutyl ether, diisopropyl ether, wherein the preferred solvent is 1,2dimethoxy ethane. The suitable base and solvent are mixed with the starting compounds of Formula (B) and (C). The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Tris(dibenzylideneacetone)dipalladium(0) at temperature ranging from 100 to 150⁰C to obtain compound of Formula (D). Step ii): A compound of Formula (E) is prepared by reacting a compound of Formula (D) with malononitrile. The reaction is carried out in the same condition as mentioned in, for example, Step ii) of Scheme I above i.e., The said reaction is performed in presence of suitable base selected from group comprising sodium tertiary butoxide, sodium hydride, lithium hydride, potassium hydride, rubidium hydride, caesium hydride, lithium aluminium hydride, wherein the preferred base is sodium tertiary butoxide or sodium hydride. The reaction is carried out in presence of a suitable catalyst selected from Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) or tris(dibenzylideneacetone)dipalladium(0), wherein the preferred catalyst is Bis(diphenylphosphino)ferrocene]dichloropalladium(II). The reaction is carried out in presence of suitable solvent selected from group comprising 1,2-dimethoxy ethane, toluene, tetrahydrofuran, diethyl ether or chlorinated solvent thereof at a temperature ranging from 100 to 150⁰C to obtain compound of Formula (E). Step iii): A compound of Formulas (A1) or (A2) is prepared by reacting a compound of Formula (E) with suitable reagents selected from a group comprising formamide (to form the compound of Formula (A1)) or guanidine (to form the compound of Formula (A2)) such as guanidine hydrochloride or guanidine carbonate. The reaction is carried out in a conventional solvent such as dimethylacetamide under heating. When formamide is a reactant, it can be also used as a solvent. The compounds obtained by the above processes can be isolated and purified by a conventional method such as pulverization, recrystallization, chromatography, and reprecipitation. Detailed synthetic protocols for preparing exemplary compounds of Formula (I) and their intermediate compounds can be referred to Examples and Preparations below or similar manners thereto or conventional manners. EXAMPLES Although the invention has been illustrated by certain of the preceding examples, it is not to be construed as being limited thereby; but rather, the invention encompasses the generic area as hereinbefore disclosed. Various modifications and embodiments can be made without departing from the spirit and scope thereof. Preparation 1: 2,3-Dibromo-5,6-dimethylpyridine:

The title compound was prepared by following the same reaction protocol as described in Zeitschrift fuer Chemie (1988), 28(2), 59-60. Preparation 2: 5-Cyclopropyl-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in WO2019213295 A1. Preparation 3: 5-Cyclobutyl-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in WO2022152821 A1 using appropriate staring materials. Preparation 4: 6-Methyl-5-(prop-1-en-2-yl)pyridin-2-amine

To a stirred solution of 5-bromo-6-methylpyridin-2-amine (5g, 26.7mmol) in dioxane (40ml) were added 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2- dioxaborolane (6.7g, 40.098mmol), K₂CO₃ (7.3g, 53.4mmol), and tetrakis(triphenylphosphine)palladium(0) (0.169g, 0.1335mmol) at 25°C. Water (8ml) was added thereto, and the resulting mixture was purged with nitrogen for 15mins. The reaction mixture was then stirred at 100°C for 16h. The reaction mixture was cooled to 25°C and diluted with EtOAc (50ml). The reaction mixture was filtered, and the filtrate was washed with water (50ml). Layers were separated and the organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo to give 4.5g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 40% of EtOAc in hexane to afford the title compound (4.1g) as a pale yellow solid. LCMS m/z = 149([M+H]⁺, 100%) Preparation 5: 5-Isopropyl-6-methylpyridin-2-amine

To a stirred solution of 6-methyl-5-(prop-1-en-2-yl)pyridin-2-amine (4.3g) in MeOH (50ml) was added Pd/C (5% wet, 0.8g) at 25°C. The resulting mixture was stirred at 25°C for 16h under hydrogen atmosphere with balloon. The reaction mixture was filtered through celite under vacuum, washed with MeOH (50ml) and the filtrate was evaporated to provide 4.1g of the crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 30% of EtOAc in hexane to afford the title compound (3.8g) as a white solid. LCMS m/z = 151 ([M+H]⁺, 100%). Preparation 6: 3-Bromo-5-fluoro-6-methylpyridin-2-amine

To a stirred solution of 5-fluoro-6-methylpyridin-2-amine (10g, 79.28mmol) in AcOH (50ml) was added bromine (4.1ml, 79.28mmol) dropwise at 25°C. The resulting mixture was stirred at 25°C for 1h. The reaction mixture was basified with aq.sat.NaHCO₃ and extracted with EtOAc (100ml x 2). Layers were separated and the combined organic layer was washed with brine (100ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 15.2g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 30% of EtOAc in hexane to afford the title compound (13.6g) as an off white solid. LCMS m/z = 205, 207 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 7: 3-Bromo-5-chloro-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-5-fluoro-6-methylpyridin-2-amine using appropriate starting materials. LCMS m/z = 221, 223, 225 (0.8:1:0.2; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 8: 3-Bromo-5-cyclopropyl-6-methylpyridin-2-amine The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-5-fluoro-6-methylpyridin-2-amine using appropriate starting materials. LCMS m/z = 227, 229 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 9: 3-Bromo-5-cyclobutyl-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-5-fluoro-6-methylpyridin-2-amine using appropriate starting materials. LCMS m/z = 241, 243 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 10: 3-bromo-5-isopropyl-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-5-fluoro-6-methylpyridin-2-amine using appropriate starting materials. LCMS m/z = 229, 231 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 11: 6-Amino-5-bromo-2,4-dimethylnicotinonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-5-fluoro-6-methylpyridin-2-amine using appropriate starting materials. LCMS m/z = 226, 228 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 12: 3-bromo-4,5,6-trimethylpyridin-2-amine

To a stirred solution of 4,5,6-trimethylpyridin-2-amine (synthesized as reported in CN107082759 A, 2g, 14.70mmol) in acetonitrile (15ml) was added NBS (8.4g, 19.11mmol) lot-wise at 0°C. The resulting mixture was stirred at 25°C for 2h. The reaction mixture was diluted with water (50ml) and extracted with EtOAc (50ml x 2). Layers were separated and the combined organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 1.8g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 10% of EtOAc in hexane to afford the title compound (1.4g) as an off white solid. LCMS m/z = 214, 216 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 13: 3-Bromo-5-fluoro-6-methylpyridin-2-ol

Sulfuric acid (9.8ml, 189mmol) was added slowly to water (100ml) at 25°C. 3- Bromo-5-fluoro-6-methylpyridin-2-amine (10.5g, 42mmol) was added thereto in one portion to get a clear solution. This solution was cooled to 0°C to 5°C with an ice-water bath. A solution of NaNO₂ (3.62g, 52.5mmol) in water (10ml) was added drop wise to the resulting suspension. The ice bath was removed, and the suspension was stirred at 25°C for 1h. A solution of 2N NaOH was added drop wise to adjust the pH 8 at a temperature < 20°C and extracted with EtOAc (100ml x 2). Layers were separated and the combined organic layer was washed with brine (100ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 7.4g of a crude compound, which was used as such for the next step. LCMS m/z = 206, 208 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 14: 3-Bromo-5-chloro-6-methylpyridin-2-ol The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-5-fluoro-6-methylpyridin-2-ol using appropriate starting materials. LCMS m/z = 222, 224 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 15: 3-bromo-5-cyclopropyl-6-methylpyridin-2-ol

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-5-fluoro-6-methylpyridin-2-ol using appropriate starting materials. LCMS m/z = 228, 230 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 16: 3-Bromo-5-cyclobutyl-6-methylpyridin-2-ol

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-5-fluoro-6-methylpyridin-2-ol using appropriate starting materials. LCMS m/z = 241, 243 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 17: 3-Bromo-5-isopropyl-6-methylpyridin-2-ol The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-5-fluoro-6-methylpyridin-2-ol using appropriate starting materials. LCMS m/z = 229, 231 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 18: 3-bromo-4,5,6-trimethylpyridin-2-ol

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-5-fluoro-6-methylpyridin-2-ol using appropriate starting materials. LCMS m/z = 215, 217 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 19: Ethyl 5,6-dibromo-2-methylnicotinate

To a stirred solution of ethyl 5-bromo-6-chloro-2-methylnicotinate (synthesized as described in WO2008085119 A1, 2.1g, 7.5mmol) in toluene (10ml) at 90°C was added a suspension of POBr₃ (4.76g, 16mmol) in toluene (10ml) and stirred for 3h. The reaction mixture was diluted with EtOAc (50ml) and washed with water (50ml). The organic layer was basified with sat.aq. NaHCO3. Layers were separated and the organic layer was washed with brine (50ml), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 2.3g of the crude title compound as a solid. LCMS m/z = 321, 323, 325 (1:2:1; [M+H]⁺, [(M+H)+2]⁺; [(M+H)+4]⁺; 100%). Preparation 20: 5,6-dibromo-2-methylnicotinic acid

To a stirred solution of ethyl 5,6-dibromo-2-methylnicotinate (0.5g, 1.55mmol) in THF (10ml) was added a solution of LiOH.H2O (391mg, 9.31mmol) in water (4ml) at 0°C and stirred at 25°C for 16h. The reaction mixture was quenched with 1N HCl (50ml) and extracted with EtOAc (25ml x 2). Layers were separated and the combined organic layer was washed with brine (50ml), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 459mg of the title compound as an off white solid. LCMS m/z = 293, 295, 297 (1:2:1; [M+H]⁺, [(M+H)+2]⁺; [(M+H)+4]⁺; 100%). Preparation 21: 5,6-dibromo-N-methoxy-N,2-dimethylnicotinamide

To a stirred solution of 5,6-dibromo-2-methylnicotinic acid (0.45g, 1.53mmol) in dichloromethane (10ml) were added N,O-dimethylhydroxylamine hydrochloride (179mg, 1.83mmol) and triethylamine (0.25ml, 1.83mmol) at 0°C. 1-ethyl-3-(3- dimethylaminopropyl)carbodiimide hydrochloride (351mg, 1.83mmol) was added thereto and stirred at 25°C for 4h. The reaction mixture was quenched with water (50ml) and extracted with EtOAc (25ml x 2). Layers were separated and the combined organic layer was washed with brine (50ml), dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo to give 0.51g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep^® column with a gradient elution of 0 to 30% of EtOAc in hexane to afford the title compound (359mg) as an off white solid. LCMS m/z = 336, 338, 340 (1:2:1; [M+H]⁺, [(M+H)+2]⁺; [(M+H)+4]⁺; 100%). Preparation 22: 1-(5,6-dibromo-2-methylpyridin-3-yl)ethan-1-one To a stirred solution of 5,6-dibromo-N-methoxy-N,2-dimethylnicotinamide (0.33g, 0.9766mmol) in anhydrous THF (10ml) was added 1M methyl magnesium bromide in THF (2.4ml) at 0°C and stirred for 2h. The resulting mixture was stirred at 25°C for 1h. The reaction mixture was quenched with sat.aq. NH4Cl (50ml) and extracted with EtOAc (25ml x 2). Layers were separated and the combined organic layer was washed with brine (50ml), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 0.25g of the title compound as a yellow liquid. LCMS m/z = 291, 293, 295 (1:2:1; [M+H]⁺, [(M+H)+2]⁺; [(M+H)+4]⁺; 100%). Preparation 23: 1-(5,6-dibromo-2-methylpyridin-3-yl)ethan-1-ol

To a stirred solution of 1-(5,6-dibromo-2-methylpyridin-3-yl)ethan-1-one (2.5g, 8.538mmol) in MeOH (25ml) was added NaBH₄ (0.419g, 11.099mmol) at 0°C. The resulting mixture was stirred at 25°C for 3h. The reaction mixture was quenched with sat.aq. NH₄Cl (100ml) and extracted with EtOAc (50ml x 2). Layers were separated and the combined organic layer was washed with brine (100ml), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 2.5g of the title compound as a yellow liquid. LCMS m/z = 293, 295, 297 (1:2:1; [M+H]⁺, [(M+H)+2]⁺; [(M+H)+4]⁺; 100%). Preparation 24: 2,3-dibromo-5-(1-methoxyethyl)-6-methylpyridine

To a stirred solution of 1-(5,6-dibromo-2-methylpyridin-3-yl)ethan-1-ol (2.5g, 8.475mmol) in anhydrous THF (30ml) was added NaH (679mg, 16.95mmol) at 0°C. After 10 min, iodomethane (0.8ml, 12.71mmol) was added drop-wise thereto and stirred at 25°C for 2h under a nitrogen atmosphere. The reaction mixture was diluted with sat. aq. NH4Cl (100ml) and extracted with EtOAc (50ml x 2). Layers were separated and the combined organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo to give 2.2g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep^® column with a gradient elution of 0 to 20% of EtOAc in hexane to afford the title compound (2g) as a pale yellow liquid. LCMS m/z = 307, 309, 311 (1:2:1; [M+H]⁺, [(M+H)+2]⁺; [(M+H)+4]⁺; 100%). Preparation 25: 2,3-dibromo-5-(1-ethoxyethyl)-6-methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-(1-methoxyethyl)-6-methylpyridine using appropriate starting materials. LCMS m/z = 321, 323, 325 (1:2:1; [M+H]⁺, [(M+H)+2]⁺; [(M+H)+4]⁺; 100%). Preparation 26: 2,3-dibromo-6-methyl-5-(1-propoxyethyl)pyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-(1-methoxyethyl)-6-methylpyridine using appropriate starting materials. LCMS m/z = 335, 337, 339 (1:2:1; [M+H]⁺, [(M+H)+2]⁺; [(M+H)+4]⁺; 100%). Preparation 27: 2-(5,6-dibromo-2-methylpyridin-3-yl)propan-2-ol

To a stirred solution of ethyl 5,6-dibromo-2-methylnicotinate (2g, 6.213mmol) in anhydrous THF (30ml) was added 2M methyl magnesium bromide in THF (24.8ml) at 0°C. The resulting mixture was stirred at 25°C for 16h. The reaction mixture was quenched with sat.aq. NH4Cl (100ml) and extracted with EtOAc (50ml x 2). Layers were separated and the combined organic layer was washed with brine (100ml), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 2.2g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 50% of EtOAc in hexane to afford the title compound (0.68g) as an off white solid. LCMS m/z = 308, 310, 312 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 28: 2,3-dibromo-5-(2-methoxypropan-2-yl)-6-methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-(1-methoxyethyl)-6-methylpyridine using appropriate starting materials. LCMS m/z = 322, 324, 326 (1:2:1, [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 29: (5,6-Dibromo-2-methylpyridin-3-yl)methanol

To a stirred solution of ethyl 5,6-dibromo-2-methylnicotinate (1.6g, 4.96mol) in THF (10ml) was added diisobutylaluminium hydride (14.9ml, 14.9mol) at -20°C and stirred for 1h. The reaction mixture was quenched with 1N HCl (50ml) and extracted with EtOAc (50ml). Layers were separated and the organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 1.3g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 20% of EtOAc in hexane to afford the title compound (0.55g) as an off white solid. LCMS m/z = 279, 281, 283 (1:2:1; [M+H]⁺, [(M+H)+2]⁺; [(M+H)+4]⁺; 100%). Preparation 30: (5,6-dibromo-2-methylpyridin-3-yl)methyl methanesulfonate

To a stirred solution of (5,6-dibromo-2-methylpyridin-3-yl)methanol (0.2g, 0.711mmol) in dichloromethane (5ml) was added triethylamine (0.198ml, 1.422mol) followed by methanesulfonyl chloride (122.33mg, 1.067mmol) at 0°C and stirred for 1h at 25°C. The reaction mixture was quenched with water (50ml) and extracted with dichloromethane (50ml). Layers were separated and the organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 0.2g of a crude compound. This crude residue was triturated with pentane (2ml) to afford the title compound (0.19g) as an off white solid. LCMS m/z = 357, 359, 361 (1:2:1; [M+H]⁺, [(M+H)+2]⁺; [(M+H)+4]⁺; 100%). Preparation 31: 2,3-dibromo-5-(bromomethyl)-6-methylpyridine

To a stirred solution of (5,6-dibromo-2-methylpyridin-3-yl)methanol (3g, 10.6799mmol) in dichloromethane (25ml) was added PBr₃ (3.48ml, 12.8158mmol) at 0°C and stirred for 2h at 25°C. The reaction mixture was quenched with sat. aq. NaHCO3 (100ml) and extracted with dichloromethane (50ml x 2). Layers were separated and the organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo to give 3.8g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 10% of EtOAc in hexane to afford the title compound (3.5g) as an orange solid. LCMS m/z = 342, 344, 346, 348 (1:3:3:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺, [(M+H)+6]⁺; 100%). Preparation 32: 2,3-Dibromo-5-fluoro-6-methylpyridine

To a stirred solution of 3-bromo-5-fluoro-6-methylpyridin-2-ol (7.4g, 36.09mmol) in DMF (22ml) and toluene (22ml) at 90°C was added POBr3 (20.64g, 72.19mmol) dissolved in toluene (15ml) dropwise over 10min. The resulting mixture was stirred at 110°C for 16h. The reaction mixture was cooled to r.t., poured into sat.aq.NaHCO₃ solution at 0°C and extracted with MTBE (100ml x 2). Layers were separated and the combined organic layer was washed with brine (100ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 8.2g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 5% of EtOAc in hexane to afford the title compound (6.1g) as an off white solid. LCMS m/z = 268, 270, 272 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 33: 2,3-Dibromo-5-chloro-6-methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-fluoro-6-methylpyridine using appropriate starting materials. LCMS m/z = 283, 285, 287 (100%). Preparation 34: 2,3-dibromo-5-cyclopropyl-6-methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-fluoro-6-methylpyridine using appropriate starting materials. LCMS m/z = 290, 292, 294 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺). Preparation 35: 2,3-Dibromo-5-cyclobutyl-6-methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-fluoro-6-methylpyridine using appropriate starting materials. LCMS m/z = 303, 305, 307 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺, 100%). Preparation 36: 2,3-dibromo-5-isopropyl-6-methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-fluoro-6-methylpyridine using appropriate starting materials. LCMS m/z = 291, 293, 295 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺, 100%). Preparation 37: 2,3-dibromo-4,5,6-trimethylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-fluoro-6-methylpyridine using appropriate starting materials. LCMS m/z = 278, 280, 282 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 38: 5,6-dibromo-2,4-dimethylnicotinonitrile A solution of 6-amino-5-bromo-2,4-dimethylnicotinonitrile (0.55g, 2.43mmol) in acetonitrile (10ml) was added sodium tert-butoxide (0.497g, 4.13mmol) and CuBr₂ (814.8mg, 3.6mmol) at 0°C and stirred for 2h. The reaction mixture was acidified with 1N HCl to pH 6 and extracted with EtOAc (20ml x 2). Layers were separated and the combined organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 0.7g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 20% of EtOAc in hexane to afford the title compound (0.25g) as an off white solid. LCMS m/z = 289, 291, 293 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 39: 5-Bromo-N,N,2-trimethylpyridin-3-amine

A solution of 5-bromo-2-methylpyridin-3-amine (2g) in a 1:1 mixture of 96% formic acid (7.5ml) and 37% aq. formaldehyde (7.5ml) was heated at reflux for 16h. The volatiles were removed under reduced pressure and the residue was neutralized with sat.aq.NaHCO₃ solution. The aqueous layer extracted with EtOAc (100ml x 2). Layers were separated and the combined organic layer was washed with brine (100ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 1.4g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 30% of EtOAc in hexane to afford the title compound (1g) as an off white solid. LCMS m/z = 215, 217 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 40: 4-(5-Bromo-2-methylpyridin-3-yl)morpholine The title compound was prepared by following the same reaction protocol as described in WO2014151616 A1. LCMS m/z = 257, 259 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 41: 5-Bromo-2-methyl-3-(piperidin-1-yl)pyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 4-(5-bromo-2-methylpyridin-3-yl)morpholine using appropriate starting materials. LCMS m/z = 255, 257 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 42: 5-Bromo-2-methyl-3-(pyrrolidin-1-yl)pyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 4-(5-bromo-2-methylpyridin-3-yl)morpholine using appropriate starting materials. LCMS m/z = 241, 243 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 43: 6-Bromo-3-methyl-2-(pyrrolidin-1-yl)pyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 4-(5-bromo-2-methylpyridin-3-yl)morpholine using appropriate starting materials. LCMS m/z = 241, 243 (1:1; [M+H]⁺, [(M+H)+2]⁺, 100%). Preparation 44: 6-Bromo-3-methyl-2-(piperidin-1-yl)pyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 4-(5-bromo-2-methylpyridin-3-yl)morpholine using appropriate starting materials. LCMS m/z = 255, 257 (1:1; [M+H]⁺, [(M+H)+2]⁺, 100%). Preparation 45: 6-Bromo-N,N,3-trimethylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 4-(5-bromo-2-methylpyridin-3-yl)morpholine using appropriate starting materials. LCMS m/z = 215, 217 (1:1; [M+H]⁺, [(M+H)+2]⁺, 100%). Preparation 46: 4-(6-Bromo-3-methylpyridin-2-yl)morpholine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 4-(5-bromo-2-methylpyridin-3-yl)morpholine using appropriate starting materials. LCMS m/z = 257, 259 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 47: 6-Bromo-2-isopropoxy-3-methylpyridine To a stirred solution of 6-bromo-2-fluoro-3-methylpyridine (0.5g, 2.6mmol) in IPA (4ml) was added potassium tert-butoxide (224mg, 5.2mmol) at r.t. and stirred at 80°C for 16h. The reaction mixture was concentrated in vacuo to give 0.38g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a elution of 100% hexane to afford the title compound (0.3g) as a colorless liquid. LCMS m/z = 230, 232 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 48: 6-Bromo-2-(4,4-difluoropiperidin-1-yl)-3-methylpyridine

To a stirred solution of 6-bromo-2-fluoro-3-methylpyridine (0.5g, 2.63mmol) in DMSO (5ml) was added K2CO3 (1.27g, 9.21mmol) at room temperature and stirred at 120°C for 16h. The reaction mixture was diluted with EtOAc (50ml) and washed with water (50ml). Layers were separated and the organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 0.75g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 5% of EtOAc in hexane to afford the title compound (0.5g) as an off white solid. LCMS m/z = 291, 293 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 49: 6-Bromo-2-(4-methoxypiperidin-1-yl)-3-methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 6-bromo-2-(4,4-difluoropiperidin-1-yl)-3- methylpyridine using appropriate starting material. LCMS m/z = 285, 287 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%) Preparation 50: 6-(6-Bromo-3-methylpyridin-2-yl)-6-azaspiro[2.5]octane

The title compound was prepared by following the same reaction protocol as described in the synthesis of 6-Bromo-2-(4,4-difluoropiperidin-1-yl)-3- methylpyridine using appropriate starting material. LCMS m/z = 281, 283 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%) Preparation 51: (R)-1-(5-Bromo-2-methylpyridin-3-yl)pyrrolidin-3-ol

To a stirred solution of 5-bromo-3-fluoro-2-methylpyridine (1g, 5.2628mmol) in NMP (6ml) was added (R)-pyrrolidin-3-ol (2.2g, 26.314mmol) at 25°C and stirred at 150°C for 16h. The reaction mixture was diluted with EtOAc (50ml) and washed with water (50ml). Layers were separated and the organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo to give 1.3g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 100% of EtOAc in hexane to afford the title compound (0.9g) as an off white solid. LCMS m/z = 257, 259 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 52: (S)-1-(5-Bromo-2-methylpyridin-3-yl)pyrrolidin-3-ol

The title compound was prepared by following the same reaction protocol as described in the synthesis of (R)-1-(5-bromo-2-methylpyridin-3-yl)pyrrolidin-3-ol using appropriate starting materials LCMS m/z = 257, 259 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 53: (S)-(1-(5-Bromo-2-methylpyridin-3-yl)pyrrolidin-2- yl)methanol

The title compound was prepared by following the same reaction protocol as described in the synthesis of (R)-1-(5-bromo-2-methylpyridin-3-yl)pyrrolidin-3-ol using appropriate starting materials. LCMS m/z = 271, 273 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 54: 5,6-Dibromo-N,N,2-trimethylpyridin-3-amine

To a stirred solution of 5-bromo-N,N,2-trimethylpyridin-3-amine (1g, 4.651mmol) in acetonitrile (10ml) was added NBS (1.07, 6.046mmol) at 0°C and stirred at 25°C for 2h. The reaction mixture was diluted with EtOAc (20ml) and washed with water (20ml). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 1.3g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 20% of EtOAc in hexane to afford the title compound (1g) as a white solid. LCMS m/z = 293, 295, 297 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 55: 4-(5,6-Dibromo-2-methylpyridin-3-yl)morpholine The title compound was prepared by following the same reaction protocol as described in the synthesis of 5,6-dibromo-N,N,2-trimethylpyridin-3-amine using appropriate starting material. LCMS m/z = 335, 337, 339 (1:2:1; [M+H]⁺,

The title compound was prepared by following the same reaction protocol as described in the synthesis of 5,6-dibromo-N,N,2-trimethylpyridin-3-amine using appropriate starting material. LCMS m/z = 333, 335, 337 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 57: 2,3-Dibromo-6-methyl-5-(pyrrolidin-1-yl)pyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 5,6-dibromo-N,N,2-trimethylpyridin-3-amine using appropriate starting material. LCMS m/z = 319, 321, 323 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 58: 2,3-Dibromo-5-methyl-6-(pyrrolidin-1-yl)pyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 5,6-dibromo-N,N,2-trimethylpyridin-3-amine using appropriate starting material. LCMS m/z = 319, 321, 323 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 59: 2,3-Dibromo-5-methyl-6-(piperidin-1-yl)pyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 5,6-dibromo-N,N,2-trimethylpyridin-3-amine using appropriate starting material. LCMS m/z = 333, 335, 337 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 60: 5,6-Dibromo-N,N,3-trimethylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 5,6-dibromo-N,N,2-trimethylpyridin-3-amine using appropriate starting material. LCMS m/z = 293, 295, 297 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 61: 4-(5,6-Dibromo-3-methylpyridin-2-yl)morpholine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 5,6-dibromo-N,N,2-trimethylpyridin-3-amine using appropriate starting material. LCMS m/z = 335, 337, 339 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 62: 2,3-Dibromo-6-isopropoxy-5-methylpyridine The title compound was prepared by following the same reaction protocol (90°C, 8h) as described in the synthesis of 5,6-dibromo-N,N,2-trimethylpyridin-3-amine using appropriate starting material. LCMS m/z = 308, 310, 312 (1:2:1; [M+H]⁺,

The title compound was prepared by following the same reaction protocol as described in the synthesis of 5,6-dibromo-N,N,2-trimethylpyridin-3-amine using appropriate starting material. LCMS m/z = 369, 371, 373 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 64: 2,3-Dibromo-6-(4-methoxypiperidin-1-yl)-5-methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 5,6-dibromo-N,N,2-trimethylpyridin-3-amine using appropriate starting material. LCMS m/z = 363, 365, 367 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 65: 6-(5,6-Dibromo-3-methylpyridin-2-yl)-6-azaspiro[2.5]octane

The title compound was prepared by following the same reaction protocol as described in the synthesis of 5,6-dibromo-N,N,2-trimethylpyridin-3-amine using appropriate starting material. LCMS m/z = 359, 361, 363 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 66: (R)-1-(5,6-dibromo-2-methylpyridin-3-yl)pyrrolidin-3-ol

The title compound was prepared by following the same reaction protocol as described in the synthesis of 5,6-dibromo-N,N,2-trimethylpyridin-3-amine using appropriate starting material. LCMS m/z = 335, 337, 339 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 67: (S)-1-(5,6-dibromo-2-methylpyridin-3-yl)pyrrolidin-3-ol

The title compound was prepared by following the same reaction protocol as described in the synthesis of 5,6-dibromo-N,N,2-trimethylpyridin-3-amine using appropriate starting material. LCMS m/z = 335, 337, 339 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 68: (S)-(1-(5,6-dibromo-2-methylpyridin-3-yl)pyrrolidin-2- yl)methanol

The title compound was prepared by following the same reaction protocol as described in the synthesis of 5,6-dibromo-N,N,2-trimethylpyridin-3-amine using appropriate starting material. LCMS m/z = 349, 351, 353 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 69: (R)-2,3-dibromo-5-(3-methoxypyrrolidin-1-yl)-6- methylpyridine

To a stirred solution of (R)-1-(5,6-dibromo-2-methylpyridin-3-yl)pyrrolidin-3-ol (0.6g) in THF (9ml) was added NaH (85mg) at 0°C, After 10min, iodomethane (380mg) was added drop-wise thereto and stirred at 25°C for 2h under a nitrogen atmosphere. The reaction mixture was diluted with water (50ml) and extracted with EtOAc (50ml). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo to give 0.550g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 20% of EtOAc in hexane to afford the title compound (0.31g) as an off white solid. LCMS m/z = 349, 351, 353 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 70: (S)-2,3-dibromo-5-(3-methoxypyrrolidin-1-yl)-6- methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of (R)-2,3-dibromo-5-(3-methoxypyrrolidin-1-yl)-6- methylpyridine using appropriate starting material. LCMS m/z = 349, 351, 353 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 71: (S)-2,3-dibromo-5-(2-(methoxymethyl)pyrrolidin-1-yl)-6- methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of (R)-2,3-dibromo-5-(3-methoxypyrrolidin-1-yl)-6- methylpyridine using appropriate starting material. LCMS m/z = 363, 365, 367 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 72: 1-(5,6-dibromo-2-methylpyridin-3-yl)pyrrolidin-3-one

To a stirred solution of (R)-1-(5,6-dibromo-2-methylpyridin-3-yl)pyrrolidin-3-ol (0.2g, 0.5952mmol) in dichloromethane (5ml) was added 1,1,1-triacetoxy-1,1- dihydro-1,2-benziodoxol-3(1H)-one (380mg, 0.8928mmol) at 0°C and stirred for 2h under a nitrogen atmosphere. The reaction mixture was diluted with dichloromethane (20ml) and washed with sat.aq. Na2SO3 (20ml) and sat.aq. NaHCO3 (20ml). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo to give 0.21g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 20% of EtOAc in hexane to afford the title compound (80mg) as an off white solid. LCMS m/z = 333, 335, 337 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 73: 2,3-Dibromo-5-isopropoxy-6-methylpyridine

A solution of isopropanol (0.1g, 1.66mmol) and potassium tert-butoxide (0.205g, 1.83mmol) in anhydrous dimethyl sulfoxide (3 ml) was stirred at r.t. for 1h. 2,3- Dibromo-5-fluoro-6-methylpyridine (0.981g, 3.66mmol) was added thereto, and the reaction mixture was stirred at r.t. overnight. The reaction mixture was diluted with EtOAc (50ml) and washed with water (20ml). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo to give 1.3g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to % of EtOAc in hexane to afford the title compound (0.1g) as a white solid. LCMS m/z = 308, 310, 312 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺). Preparation 74: 2,3-Dibromo-5-(cyclopropylmethoxy)-6-methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-isopropoxy-6-methylpyridine using appropriate starting material. LCMS m/z = 320, 322, 324 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺, 100%). Preparation 75: 2,3-Dibromo-5-cyclobutyloxy-6-methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-isopropoxy-6-methylpyridine using appropriate starting material. LCMS m/z = 320, 322, 324 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 76: 2,3-Dibromo-6-methyl-5-(2,2,2-trifluoroethoxy)pyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-isopropoxy-6-methylpyridine using appropriate starting material. LCMS m/z = 348, 350, 352 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 77: 2,3-Dibromo-6-methyl-5-(1H-pyrazol-1-yl)pyridine

A stirred solution of 2,3-dibromo-5-fluoro-6-methylpyridine (0.6g, 2.231mmol), 1H-pyrazole (182mg, 2.677mmol), and potassium carbonate (461.8mg, 3.346mmol) in 2 mL of dimethyl sulfoxide was heated at 120°C for 2h under a nitrogen atmosphere. The reaction mixture was diluted with water (50ml) and extracted with EtOAc (50ml). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 20% of EtOAc in hexane to afford the title compound (0.19g) as a white solid. LCMS m/z = 316, 318, 320 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 78: 2,3-Dibromo-5-(methoxymethyl)-6-methylpyridine

To a stirred solution of (5,6-dibromo-2-methylpyridin-3-yl)methanol (270mg, 0.96mol) in THF (5ml) was added NaH (46.08mg, 1.93mol) at 0°C and stirred for 1h. Methyl iodide (0.08ml, 1.44mol) was added thereto and stirred at 25°C for 16h. The reaction mixture was diluted with EtOAc (20ml) and washed with water (20ml). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 0.3g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 20% of EtOAc in hexane to afford the title compound (0.24g) as an off white solid. LCMS m/z = 294, 296, 298 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 79: 2,3-Dibromo-5-(ethoxymethyl)-6-methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-(methoxymethyl)-6-methylpyridine using appropriate starting material. LCMS m/z = 308, 310, 312 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 80: 2,3-Dibromo-5-(methoxymethyl)-4,6-dimethylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-(methoxymethyl)-6-methylpyridine using appropriate starting material. LCMS m/z = 308, 310, 312 (1:2:1; ([M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 81: 2,3-Dibromo-5-(isopropoxymethyl)-6-methylpyridine

To IPA (2ml) was added NaH (10mg, 0.2757mmol) at 0°C and stirred for 10min. (5,6-Dibromo-2-methylpyridin-3-yl)methyl methanesulfonate (90mg, 0.2506mmol) was added thereto and stirred at 25°C for 1h and then at 50°C for 1h. The reaction mixture was diluted with EtOAc (20ml) and washed with water (20ml). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 70mg of a crude compound as an off white solid. LCMS m/z = 321, 323, 325 (1:2:1; ([M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 82: 2,3-Dibromo-6-methyl-5-((2,2,2 trifluoroethoxy)methyl)pyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-(isopropoxymethyl)-6-methylpyridine using appropriate starting materials and THF as a solvent. LCMS m/z = 361, 363, 365 (1:2:1; ([M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 83: 2,3-Dibromo-5-(cyclobutoxymethyl)-6-methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2,3-dibromo-5-(isopropoxymethyl)-6-methylpyridine using appropriate starting materials and THF as a solvent. LCMS m/z = 333, 335, 337 (1:2:1; ([M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 84: (S)-2,3-Dibromo-5-(3-fluoropyrrolidin-1-yl)-6- methylpyridine To a stirred solution of (R)-1-(5,6-dibromo-2-methylpyridin-3-yl)pyrrolidin-3-ol (200mg, 0.5952mmol) in dichloromethane (3ml) was added (diethylamino)sulfur trifluoride (191.8mg, 1.1904mmol) at 0°C and stirred for 2h. The reaction mixture was quenched with sat.aq. NaHCO3 (25ml) and extracted with dichloromethane (25ml). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 0.12g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 10% of EtOAc in hexane to afford the title compound (80mg) as an off white solid. LCMS m/z = 336, 338, 340 (1:2:1; ([M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 85: (R)-2,3-Dibromo-5-(3-fluoropyrrolidin-1-yl)-6- methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of (S)-2,3-dibromo-5-(3-fluoropyrrolidin-1-yl)-6- methylpyridine using appropriate starting materials. LCMS m/z = 336, 338, 340 (1:2:1; ([M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 86: 2,3-dibromo-5-(3,3-difluoropyrrolidin-1-yl)-6-methylpyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of (S)-2,3-Dibromo-5-(3-fluoropyrrolidin-1-yl)-6- methylpyridine using 1-(5,6-dibromo-2-methylpyridin-3-yl)pyrrolidin-3-one as a starting material. LCMS m/z = 354, 356, 358 (1:2:1; ([M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 87: 2,3-Dibromo-5-((3,3-difluoropyrrolidin-1-yl)methyl)-6- methylpyridine

To a stirred solution of 3,3-difluoropyrrolidine hydrochloride (367.41mg, 2.559mmol) was added potassium carbonate (707.44mg, 5.1186mmol) at 0°C. After 10min, 2,3-dibromo-5-(bromomethyl)-6-methylpyridine (800mg, 2.3266mmol) was added thereto at 0°C and stirred for 2h. The reaction mixture was quenched with water (50ml) and extracted with EtOAc (50ml). Layers were separated and the organic layer was washed with brine (50ml). The organic layer was dried over anhydrous sodium sulphate, filtered, and concentrated in vacuo to give 1.1g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 10% of EtOAc in hexane to afford the title compound (600mg) as an off white solid. LCMS m/z = 368, 370, 372 (1:2:1; ([M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 88: 1-(5,6-Dibromo-2-methylpyridin-3-yl)-N,N- dimethylmethanamine

To a stirred solution of 2,3-dibromo-5-(bromomethyl)-6-methylpyridine (750mg, 2.1812mmol) in THF (10ml) was added aq. dimethylamine (295mg, 6.5437mmol) at 0°C and stirred at 25°C for 16h. The reaction mixture was quenched with water (50ml) and extracted with EtOAc (50ml). Layers were separated and the organic layer was washed with brine (50ml). The organic layer was dried over anhydrous sodium sulphate, filtered, and concentrated in vacuo to give 1.05g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 10% of EtOAc in hexane to afford the title compound (640mg) as an off white solid. LCMS m/z = 306, 308, 310 (1:2:1; ([M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 89: 2,3-Dibromo-6-methyl-5-(pyrrolidin-1-ylmethyl)pyridine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 1-(5,6-dibromo-2-methylpyridin-3-yl)-N,N- dimethylmethanamine using appropriate starting materials. LCMS m/z = 332, 334, 336 (1:2:1; ([M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 90: 2,6-Dichloro-3,5-dimethoxyaniline:

The title compound was prepared by following the same reaction protocol as described in Journal of Medicinal Chemistry (2011), 54(20), 7066-7083. Preparation 91: 2,6-Dibromo-3,5-dimethoxyaniline:

The title compound was prepared by following similar reaction protocol as described in Chemosphere (2013), 92(3), 286-292. Preparation 92: 3,5-Dimethoxy-2,6-dimethylaniline: To a stirred solution of 2,6-dibromo-3,5-dimethoxyaniline (0.75g, 2.412mmol) in dioxane (10ml) were added trimethylboroxine (908mg, 7.237mmol), PdCl2dppf.CH2Cl2 (133mg, 0.2412mmol), and cesium carbonate (2.3g, 7.237mmol) at 25°C. The reaction mixture was degassed with nitrogen gas for 15min. The resulting mixture was stirred at 100°C for 1h in microwave reactor. The reaction mixture was diluted with EtOAc (20ml) and washed with water (20ml). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo to give 0.8g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 30% of EtOAc in hexane to afford the title compound (0.25g) as an off white solid. LCMS m/z = 182 ([M+H]⁺, 100%). Preparation 93: 3-Methoxy-2,6-dimethylaniline: The title compound was prepared by following the same reaction protocol as described in US4564640A. Preparation 94: 2,4-Dimethyl-3-nitrophenol

The title compound was prepared by following the same reaction protocol as described in EP0887346A2. Preparation 95: 1-((4-Methoxybenzyl)oxy)-2,4-dimethyl-3-nitrobenzene To a stirred solution of 2,4-dimethyl-3-nitrophenol (2.2g, 31.173mmol) in DMF (20ml) at 0°C were added cesium carbonate (5.8g, 19.75mmol) and p- methoxybenzyl chloride (2.6g, 17.125mmol) at 25°C. The resulting mixture was stirred at 70°C for 16h. The reaction mixture was diluted with EtOAc (50ml) and washed with water (50ml). Layers were separated and the organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 2.5g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 20% of EtOAc in hexane to afford the title compound (2.1g) as an off white solid. LCMS m/z = 288 [M+H]⁺. Preparation 96: 3-((4-Methoxybenzyl)oxy)-2,6-dimethylaniline

To a stirred solution of 1-((4-methoxybenzyl)oxy)-2,4-dimethyl-3-nitrobenzene (1.5g, 5.22mmol) in MeOH (20ml) at 0°C was added NaBH₄ (794mg, 20.9mmol) followed by NiCl2 (123mg, 0.523mmol) lot-wise over 10min. The resulting mixture was stirred at 25°C for 2h. The reaction mixture was diluted with EtOAc (50ml) and washed with water (50ml). Layers were separated and the organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo to afford the title compound (1g) as an off white solid. LCMS m/z = 258 ([M+H]⁺, 100%). Preparation 97: 3-Bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine: A mixture of 2,3-dibromo-5,6-dimethylpyridine (400mg, 1eqv.) and 2,6-dichloro- 3,5-dimethoxyaniline (302mg, 0.9eqv.) in dimethoxyethane (10ml) was stirred in a sealed tube. Cesium carbonate (1.47g, 3 eqv.) was added thereto and degassed with nitrogen gas for 10min. Xantphos (131mg, 0.15eqv.) and Pd2dba3 (111mg, 0.08eqv.) were added thereto and again degassed with nitrogen gas for 10 min. The resulting mixture was stirred at 90°C for 16h. The reaction mixture was diluted with EtOAc (20ml) and washed with water (20ml). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo to give 0.72g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 40% of EtOAc in hexane to afford the title compound (0.4g, 65%) as a white solid. LCMS m/z = 405, 407, 409 ([M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺). Preparation 98: 3-Bromo-N-(2,6-dibromo-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine:

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 493, 495, 497, 499 ([M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺ , [(M+H)+6]⁺). Preparation 99: 3-Bromo-N-(3,5-dimethoxy-2,6-dimethylphenyl)-5,6- dimethylpyridin-2-amine:

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 365, 367 (1:1, [M+H]⁺, [(M+H)+2]⁺; 100%) Preparation 100: 3-Bromo-N-(3,5-dimethoxyphenyl)-5,6-dimethylpyridin-2- amine:

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 337, 339 (1:1, [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 101: 3-Bromo-N-(3-methoxy-2,6-dimethylphenyl)-5,6- dimethylpyridin-2-amine:

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 335, 337 (1:1, [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 102: 3-Bromo-5-fluoro-N-(3-methoxy-2,6-dimethylphenyl)-6- methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 339, 341 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 103: 3-Bromo-5-chloro-N-(3-methoxy-2,6-dimethylphenyl)-6-

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 355, 357, 359 ([M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺) Preparation 104: 3-Bromo-5-cyclopropyl-N-(3-methoxy-2,6-dimethylphenyl)- 6-methylpyridin-2-amine The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 361, 363 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 105: 3-Bromo-N²-(3-methoxy-2,6-dimethylphenyl)-N⁵,N⁵,6- trimethylpyridine-2,5-diamine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 364, 366 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 106: 3-Bromo-N-(3-methoxy-2,6-dimethylphenyl)-6-methyl-5- (piperidin-1-yl)pyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 404, 406 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 107: 3-Bromo-N-(3-methoxy-2,6-dimethylphenyl)-6-methyl-5- (morpholin-4-yl)pyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 406, 408 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 108: 3-Bromo-N-(3-methoxy-2,6-dimethylphenyl)-6-methyl-5- (pyrrolidin-1-yl)pyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 390, 392 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 109: 3-Bromo-N-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 5-methyl-6-(pyrrolidin-1-yl)pyridin-2-amine The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z =496,

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 509, 511 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 111: 3-Bromo-N²-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-N⁶,N⁶,5-trimethylpyridine-2,6-diamine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 470, 472 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 112: 3-Bromo-N-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 5-methyl-6-(morpholin-4-yl)pyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 511, 513 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 113: 3-Bromo-5-isopropoxy-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 485,

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 493, 495 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 115: 3-Bromo-5-cyclobutyl-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 481, 483 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 116: 3-Bromo-5-isopropyl-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 469, 471 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 117: 3-Bromo-5-(cyclopropylmethoxy)-N-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methylpyridin-2-amine The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 497, 499 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 118: 3-Bromo-5-cyclobutoxy-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 497, 499 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 119: 3-Bromo-6-isopropoxy-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-5-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 485, 487 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%) Preparation 120: 3-Bromo-6-(4,4-difluoropiperidin-1-yl)-N-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-5-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 546, 548 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%) Preparation 121: 3-Bromo-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-6-(4-methoxypiperidin-1-yl)-5-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 540, 542 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 122: 3-Bromo-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-5-methyl-6-(6-azaspiro[2.5]octan-6-yl)pyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 536, 538 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 123: 3-Bromo-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-5-(methoxymethyl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 471, 473 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 124: 3-Bromo-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-5-(1-methoxyethyl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 485, 487 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). This racemic compound was purified by chiral preparative HPLC to give two enantiomers as shown below.

Preparation 125: 3-Bromo-5-(1-ethoxyethyl)-N-(3-((4-methoxybenzyl)oxy)- 2,6-dimethylphenyl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 499, 501 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). This racemic compound was purified by chiral preparative HPLC to give two enantiomers as shown below.

Preparation 126: 3-Bromo-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-6-methyl-5-(1-propoxyethyl)pyridin-2-amine The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 512, 514 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). This racemic compound was purified by chiral preparative HPLC to give two enantiomers as shown below.

Preparation 127: 3-Bromo-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-5-(2-methoxypropan-2-yl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 499, 501 (1:1; [M+H]⁺, [(M+H)+2]⁺; 50%). Preparation 128: (S)-3-Bromo-5-(3-fluoropyrrolidin-1-yl)-N-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 514, 516 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 129: (R)-3-Bromo-5-(3-fluoropyrrolidin-1-yl)-N-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 514, 516 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 130: 3-Bromo-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-6-methyl-5-(2,2,2-trifluoroethoxy)pyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 525, 527 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 131: 5-Bromo-6-((3-methoxy-2,6-dimethylphenyl)amino)-2,4- dimethylnicotinonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 360, 362 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 132: 3-Bromo-N-(3-methoxy-2,6-dimethylphenyl)-4,5,6- trimethylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 349, 351 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 133: (R)-1-(5-Bromo-6-((3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)amino)-2-methylpyridin-3-yl)pyrrolidin-3-ol

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 512, 514 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 134: (R)-3-Bromo-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-5-(3-methoxypyrrolidin-1-yl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 526, 528 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 135: (S)-3-Bromo-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-5-(3-methoxypyrrolidin-1-yl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 526, 528 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 136: (S)-3-Bromo-N-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-5-(2-(methoxymethyl)pyrrolidin-1-yl)-6-methylpyridin-2- amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 540, 542 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 137: 3-Bromo-5-(3,3-difluoropyrrolidin-1-yl)-N-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 532, 534 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 138: 3-bromo-5-((3,3-difluoropyrrolidin-1-yl)methyl)-N-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 546, 548 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 139: 3-bromo-5-((dimethylamino)methyl)-N-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 484, 486 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 140: 3-bromo-N-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 6-methyl-5-(pyrrolidin-1-ylmethyl)pyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 510,

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 485, 487 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 142: 3-Bromo-5-(isopropoxymethyl)-N-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methylpyridin-2-amine The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 499, 501 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 143: 3-Bromo-N-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 5-(methoxymethyl)-4,6-dimethylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 485, 487 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 144: 3-Bromo-N-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 6-methyl-5-((2,2,2-trifluoroethoxy)methyl)pyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 539, 541 (1:1; [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 145: 3-Bromo-5-(cyclobutoxymethyl)-N-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methylpyridin-2-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine using appropriate starting materials. LCMS m/z = 511,

In a sealed tube, a mixture of malononitrile (0.13g, 1.9696mmol) and sodium tert- butoxide (0.189g, 1.9687mmol) in dimethoxyethane was degassed by purging nitrogen gas for 30 min. 3-Bromo-N-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethylpyridin-2-amine (0.2g, 0.4925mmol) was added thereto and the resulting mixture was degassed by purging nitrogen gas for 10min. PdCl2dppf.CH2Cl2 (40mg, 0.049mmol) was added and again degassed the mixture with nitrogen gas for 10min. The resulting mixture was stirred at 100°C for 16h. The resulting mixture was cooled to 25°C and concentrated in vacuo to give 0.75g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep^® column with a gradient elution of 0 to 50% of EtOAc in hexane to afford the title compound (0.25g) as an off-white solid. LCMS m/z = 391, 393 ([M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 147: 2-Amino-1-(2,6-dibromo-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 478, 480, 482 (1:2:1; [M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 148: 2-Amino-1-(3,5-dimethoxy-2,6-dimethylphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 351 ([M+H]⁺; 100%). Preparation 149: 2-Amino-1-(3,5-dimethoxyphenyl)-5,6-dimethyl-1H- pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 323 ([M+H]⁺; 100%). Preparation 150: 2-Amino-1-(3-methoxy-2,6-dimethylphenyl)-5,6-dimethyl- 1H-pyrrolo[2,3-b]pyridine-3-carbonitrile:

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z =321 ([M+H]⁺; 100%). Preparation 151: 2-Amino-5-fluoro-1-(3-methoxy-2,6-dimethylphenyl)-6- methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 325([M+H]⁺; 100%) Preparation 152: 2-Amino-5-chloro-1-(3-methoxy-2,6-dimethylphenyl)-6- methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 341, 343 (1:3, [M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 153: 2-Amino-5-cyclopropyl-1-(3-methoxy-2,6-dimethylphenyl)- 6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 347 ([M+H]⁺; 100%). Preparation 154: 2-Amino-5-(dimethylamino)-1-(3-methoxy-2,6- dimethylphenyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 350 ([M+H]⁺; 100%). Preparation 155: 2-Amino-1-(3-methoxy-2,6-dimethylphenyl)-6-methyl-5- (piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 390([M+H]⁺; 100%). Preparation 156: 2-Amino-1-(3-methoxy-2,6-dimethylphenyl)-6-methyl-5- (morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 392 ([M+H]⁺; 100%). Preparation 157: 2-Amino-1-(3-methoxy-2,6-dimethylphenyl)-6-methyl-5- (pyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 376 ([M+H]⁺; 100%). Preparation 158: 2-Amino-1-(3-methoxy-2,6-dimethylphenyl)-4,6-dimethyl- 1H-pyrrolo[2,3-b]pyridine-3,5-dicarbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 346 ([M+H]⁺; 100%). Preparation 159: 2-Amino-1-(3-methoxy-2,6-dimethylphenyl)-4,5,6-trimethyl- 1H-pyrrolo[2,3-b]pyridine-3-carbonitrile The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 335 ([M+H]⁺; 100%). Preparation 160: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 5-methyl-6-(pyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 482 ([M+H]⁺; 100%). Preparation 161: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 5-methyl-6-(piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 496 ([M+H]⁺; 100%). Preparation 162: 2-Amino-6-(dimethylamino)-1-(3-((4-methoxybenzyl)oxy)- 2,6-dimethylphenyl)-5-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 456 ([M+H]⁺; 100%). Preparation 163: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 5-methyl-6-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 498 ([M+H]⁺; 100%). Preparation 164: 2-Amino-5-isopropoxy-1-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 471 ([M+H]⁺; 100%). Preparation 165: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 6-methyl-5-(1H-pyrazol-1-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 479 ([M+H]⁺; 100%). Preparation 166: 2-Amino-5-cyclobutyl-1-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 467 ([M+H]⁺; 100%). Preparation 167: 2-Amino-5-isopropyl-1-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 455 ([M+H]⁺; 100%). Preparation 168: 2-Amino-5-(cyclopropylmethoxy)-1-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methyl-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 483 ([M+H]⁺; 100%). Preparation 169: 2-Amino-5-cyclobutoxy-1-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 483 ([M+H]⁺; 100%). Preparation 170: 2-Amino-6-isopropoxy-1-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-5-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 471 ([M+H]⁺; 100%). Preparation 171: 2-Amino-6-(4,4-difluoropiperidin-1-yl)-1-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-5-methyl-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 532 ([M+H]⁺; 100%). Preparation 172: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 6-(4-methoxypiperidin-1-yl)-5-methyl-1H-pyrrolo[2,3-b]pyridine-3- carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 526 [M+H]⁺; 100%). Preparation 173: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 5-methyl-6-(6-azaspiro[2.5]octan-6-yl)-1H-pyrrolo[2,3-b]pyridine-3-

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 522 ([M+H]⁺; 100%). Preparation 174: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 5-(methoxymethyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 457 ([M+H]⁺; 100%). Preparation 175: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 5-(1-methoxyethyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (Isomer-I)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 471 ([M+H]⁺; 100%). Preparation 176: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 5-(1-methoxyethyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (Isomer-II)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 471 ([M+H]⁺; 100%). Preparation 177: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 5-(2-methoxypropan-2-yl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 485 ([M+H]⁺; 100%). Preparation 178: 2-Amino-5-(1-ethoxyethyl)-1-(3-((4-methoxybenzyl)oxy)- 2,6-dimethylphenyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (Isomer-I)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 485 ([M+H]⁺; 100%). Preparation 179: 2-Amino-5-(1-ethoxyethyl)-1-(3-((4-methoxybenzyl)oxy)- 2,6-dimethylphenyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (Isomer-II)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 485 ([M+H]⁺; 100%). Preparation 180: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 6-methyl-5-(1-propoxyethyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (Isomer-I)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 499 ([M+H]⁺; 100%). Preparation 181: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 6-methyl-5-(1-propoxyethyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (Isomer-II) The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 499 ([M+H]⁺; 100%). Preparation 182: (S)-2-Amino-5-(3-fluoropyrrolidin-1-yl)-1-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methyl-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 500 ([M+H]⁺; 100%). Preparation 183: (R)-2-Amino-5-(3-fluoropyrrolidin-1-yl)-1-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methyl-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 500 ([M+H]⁺; 100%). Preparation 184: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 6-methyl-5-(2,2,2-trifluoroethoxy)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 511 ([M+H]⁺; 100%). Preparation 185: (R)-2-Amino-5-(3-hydroxypyrrolidin-1-yl)-1-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methyl-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 498 ([M+H]⁺; 100%). Preparation 186: (R)-2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-5-(3-methoxypyrrolidin-1-yl)-6-methyl-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 512 ([M+H]⁺; 100%). Preparation 187: (S)-2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-5-(3-methoxypyrrolidin-1-yl)-6-methyl-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = LCMS m/z = 512 ([M+H]⁺; 100%). Preparation 188: (S)-2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-5-(2-(methoxymethyl)pyrrolidin-1-yl)-6-methyl-1H- pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 526 ([M+H]⁺; 100%). Preparation 189: 2-Amino-5-(3,3-difluoropyrrolidin-1-yl)-1-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methyl-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 518 ([M+H]⁺; 100%). Preparation 190: 2-Amino-5-((3,3-difluoropyrrolidin-1-yl)methyl)-1-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methyl-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 532 ([M+H]⁺; 100%). Preparation 191: 2-Amino-5-((dimethylamino)methyl)-1-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methyl-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 470 ([M+H]⁺; 100%). Preparation 192: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 6-methyl-5-(pyrrolidin-1-ylmethyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 496 ([M+H]⁺; 100%). Preparation 193: 2-Amino-5-(ethoxymethyl)-1-(3-((4-methoxybenzyl)oxy)- 2,6-dimethylphenyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 471 ([M+H]⁺; 100%). Preparation 194: 2-Amino-5-(isopropoxymethyl)-1-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methyl-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 485 ([M+H]⁺; 100%). Preparation 195: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 5-(methoxymethyl)-4,6-dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 471 ([M+H]⁺; 100%). Preparation 196: 2-Amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 6-methyl-5-((2,2,2-trifluoroethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine-3- carbonitrile

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 525 ([M+H]⁺; 100%). Preparation 197: 2-Amino-5-(cyclobutoxymethyl)-1-(3-((4- methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-methyl-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile using appropriate starting materials. LCMS m/z = 497 ([M+H]⁺; 100%). Preparation 198: 2-Amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide:

A solution of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6-dimethyl-1H- pyrrolo[2,3-b]pyridine-3-carbonitrile (200 mg) in sulfuric acid (1 mL) was stirred at r.t. for 1h. The mixture was then slowly poured into cold water (10ml) with vigorous stirring and then made slightly alkaline with the addition of concentrated aq. NH₄OH. The reaction mixture was extracted with EtOAc (20ml) and washed with water (10ml x 2). The layers were separated, and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 0.21g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep^® column with a gradient elution of 0 to 5% of MeOH in dichloromethane to afford the title compound (0.11g) as an off white solid. LCMS m/z = 409, 411 ([M+H]⁺, [(M+H)+2]⁺; 100%). Preparation 199: 2-Amino-1-(2,6-dibromo-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide using an appropriate starting material. LCMS m/z = 497, 499, 501 ([M+H]⁺, [(M+H)+2]⁺, [(M+H)+4]⁺; 100%). Preparation 200: 2-Amino-1-(3,5-dimethoxy-2,6-dimethylphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide using an appropriate starting material. LCMS m/z = 369 ([M+H]⁺; 100%). Preparation 201: 2-Amino-1-(3,5-dimethoxyphenyl)-5,6-dimethyl-1H- pyrrolo[2,3-b]pyridine-3-carboxamide:

The title compound was prepared by following the same reaction protocol as described in the synthesis of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide using an appropriate starting material. LCMS m/z = 341 ([M+H]⁺; 100%). Preparation 202: 9-(3-Methoxy-2,6-dimethylphenyl)-6,7-dimethyl-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4-amine

A solution of 2-amino-1-(3-methoxy-2,6-dimethylphenyl)-5,6-dimethyl-1H- pyrrolo[2,3-b]pyridine-3-carbonitrile (100 mg) in formamide (1 mL) was stirred at 200°C for 3h. The mixture was cooled to r.t. and then slowly poured into cold water (10ml) with vigorous stirring. The precipitated solid was filtered on Buchner funnel, dried azeotropically with toluene to give the title compound (0.15g) as a solid, which was used as such for next step. LCMS m/z = 348 ([M+H]⁺; 100%). Compounds of the Preparations in Table 2 were synthesized by following an analogous reaction protocol as used for the preparation of 9-(3-methoxy-2,6- dimethylphenyl)-6,7-dimethyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4- amine (Preparation 202) above using an appropriate starting material. Table 2: Preparations using reaction protocols analogous to Preparation 202.

Preparation 212: 9-(3-Methoxy-2,6-dimethylphenyl)-6,7-dimethyl-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidine-2,4-diamine:

To a stirred solution of 2-amino-1-(3-methoxy-2,6-dimethylphenyl)-5,6-dimethyl- 1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (50 mg, 0.1562mmol) in dimethylacetamide (1.5 mL) was added guanidine carbonate (84.37, 0.4687mmol) at r.t. and stirred at 150°C for 16h. The reaction mixture was diluted with EtOAc (10ml) and washed with water (10ml x 2). Layers were separated and the organic layer was washed with brine (20ml). The organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo to give 0.12g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 5% of MeOH in dichloromethane to afford the title compound (40mg) as an off-white solid. LCMS m/z = 363 ([M+H]⁺; 100%). Preparation 213: 9-(3-((4-Methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-(1- methoxyethyl)-7-methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4- amine (Isomer-II)

A stirred solution of 2-amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)- 5-(1-methoxyethyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (Isomer- II) (850mg) in triethyl orthoformate (15mL) was heated to 150°C for 24h. The reaction mixture was concentrated in vacuo and the residue was dissolved in MeOH (10ml).7N NH₃ in MeOH (4ml) was added at 0°C and the resulting mixture was stirred at 25°C for 1h. The reaction mixture was concentrated in vacuo and this crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 50% of EtOAc in hexane to afford the title compound (500mg) as an off white solid. LCMS: m/z = 498 ([M+H]⁺; 100%). Preparation 214: 9-(3-((4-Methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-(1- methoxyethyl)-7-methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4- amine (Isomer-I)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 9-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-6- (1-methoxyethyl)-7-methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4-amine (Isomer-II) using 2-amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-5- (1-methoxyethyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (Isomer-I) as a starting material. LCMS m/z = 498 ([M+H]⁺; 100%). Preparation 215: 9-(3-((4-Methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-(2- methoxypropan-2-yl)-7-methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin- 4-amine

The title compound was prepared by following the same reaction protocol as described in the synthesis of 9-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-6- (1-methoxyethyl)-7-methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4-amine (Isomer-II) using an appropriate starting material. LCMS m/z = 512 ([M+H]⁺; 100%). Preparation 216: 6-(1-Ethoxyethyl)-9-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-7-methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4- amine (Isomer-I)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 9-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-6- (1-methoxyethyl)-7-methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4-amine (Isomer-II) using 2-amino-5-(1-ethoxyethyl)-1-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (Isomer-I) as a starting material. LCMS m/z = 512 ([M+H]⁺; 100%). Preparation 217: 6-(1-Ethoxyethyl)-9-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-7-methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4- amine (Isomer-II)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 9-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-6- (1-methoxyethyl)-7-methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4-amine (Isomer-II) using 2-amino-5-(1-ethoxyethyl)-1-(3-((4-methoxybenzyl)oxy)-2,6- dimethylphenyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (Isomer-II) as a starting material. LCMS m/z = 512 ([M+H]⁺; 100%). Preparation 218: 9-(3-((4-Methoxybenzyl)oxy)-2,6-dimethylphenyl)-7- methyl-6-(1-propoxyethyl)-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4- amine (Isomer-I)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 9-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-6- (1-methoxyethyl)-7-methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4-amine (Isomer-II) using 2-amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-6- methyl-5-(1-propoxyethyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (Isomer-I) as a starting material. LCMS m/z = 526 ([M+H]⁺; 100%). Preparation 219: 9-(3-((4-Methoxybenzyl)oxy)-2,6-dimethylphenyl)-7- methyl-6-(1-propoxyethyl)-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4- amine (Isomer-II)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 9-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-6- (1-methoxyethyl)-7-methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4-amine (Isomer-II) using 2-amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-6- methyl-5-(1-propoxyethyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (Isomer-II) as a starting material. LCMS m/z = 526 ([M+H]⁺; 100%). The following examples provide the process of synthesizing the compounds of Formula (I) as provided in Table 1 as above. Example 1: 2-Amino-1-(2,6-dichloro-3,5-dihydroxyphenyl)-5,6-dimethyl-1H- pyrrolo[2,3-b]pyridine-3-carboxamide.

To a stirred solution of 2-amino-1-(2,6-dichloro-3,5-dimethoxyphenyl)-5,6- dimethyl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide (160 mg, 0.39mmol) prepared in Preparation 198, in dichloromethane (3 mL) was added 1M BBr₃ in dichloromethane (3.9ml, 3.90mmol) at 0°C and stirred at r.t. for 16h. The mixture was then slowly quenched with MeOH (5ml) with vigorous stirring and then concentrated in vacuo to give 0.156g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 7% of MeOH in dichloromethane to afford the title compound (0.023g) as an off white solid. ¹H NMR (400MHz, DMSO-d₆) ^ 10.57(s, 2H), 7.79(s, 1H), 6.99(s, 2H), 6.87(s, 1H), 6.63(s, 2H), 2.25(s, 3H), 2.24(s, 3H); LCMS m/z = 381, 383 ([M+H]⁺, [(M+H)+2]⁺; 100%).. Compounds of the Examples in Table 3 were synthesized by following an analogous reaction protocol as was used for the preparation of 2-amino-1-(2,6- dichloro-3,5-dihydroxyphenyl)-5,6-dimethyl-1H-pyrrolo[2,3-b]pyridine-3- carboxamide using an appropriate starting material. Table 3: Examples using the reaction protocols analogous to Example 1

Example 16: 3-(4-Amino-6-methyl-7-(pyrrolidin-1-yl)-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-9-yl)-2,4-dimethylphenol

A mixture of 2-amino-1-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-5- methyl-6-(pyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (160mg, 1.811mmol) in formamide (2 mL) was heated at 200°C for 3h. The reaction mixture was cooled to r.t. and ice-cold water was added slowly thereto with vigorous stirring. The precipitated solid was collected by filtration on Buchner funnel under vacuum. The residue was dissolved in 10% MeOH in dichloromethane and purified by combiflash instrument onto a redisep^® column with an isocratic elution of 5% MeOH in dichloromethane to afford 0.45g of solid, which was further purified by preparative HPLC to provide the title compound (0.010g) as an off white solid.¹H NMR (DMSO-d₆) ^ 9.35 (s, 1H), 8.38(s, 1H), 8.08(s, 1H), 7.06(bs, 2H), 7.00(d, J = 8.4 Hz, 1H), 6.86(d, J = 8.4 Hz, 1H), 3.35(m, 4H), 2.43(s, 3H), 1.80(m, 4H), 1.69(s, 3H), 1.59(s, 3H); LCMS m/z = 389 [M+H]⁺. Compounds of the Examples in Table 4 was synthesized by following an analogous reaction protocol as described in the preparation of 3-(4-amino-6-methyl-7- (pyrrolidin-1-yl)-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-9-yl)-2,4- dimethylphenol using an appropriate starting material and reaction time (3h to 12h). Table 4: Examples using reaction protocol analogous to Example 16

Example 49: 3-(4-Amino-6-ethyl-7-methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3- d]pyrimidin-9-yl)-2,4-dimethylphenol

To a stirred solution of 3-(4-amino-7-methyl-6-vinyl-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-9-yl)-2,4-dimethylphenol (30mg) in MeOH (2ml) was added 5% Pd/C (20mg) at 25°C and stirred for 16h under a hydrogen atmosphere using balloon. The reaction mixture was filtered through celite bed under vacuum. The filtrate was concentrated in vacuo to give 32mg of a crude compound. This crude residue was purified by reverse phase preparative HPLC to afford the title compound (3mg) as an off white solid. ¹H NMR (DMSO- d6) ^ 9.51 (s, 1H), 8.58 (s, 1H), 8.19 (s, 1H), 7.39 (bs, 2H), 7.04 (d, J = 8.0 Hz, 1H), 6.91 (d, J = 8.0 Hz, 1H), 2.75 (q, J = 7.6 Hz, 2H), 2.49 (s, 3H), 1.65 (s, 3H), 1.55 (s, 3H), 1.29 (t, J = 7.6 Hz, 3H); LCMS m/z = 348 [M+H]⁺ Example 50: 3-(4-Amino-6-(1-methoxyethyl)-7-methyl-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-9-yl)-2,4-dimethylphenol (Isomer-II)

To a stirred solution of 9-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-(1- methoxyethyl)-7-methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4-amine (Isomer-II, 500mg) in MeOH (10mL) was added 4M HCl in dioxane (2ml) at 0°C. The resulting mixture was stirred at 25°C for 16h. The reaction mixture was basified with sat.aq. NaHCO₃ (50ml) at 0°C and extracted with EtOAc (25ml x 2). Layers were separated and the combined organic layer was washed with brine (50ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 0.62g of a crude compound. This crude residue was purified by combiflash instrument onto a redisep® column with a gradient elution of 0 to 50% of EtOAc in hexane to afford the title compound (215mg) as an off-white solid. ¹H NMR (DMSO-d6) ^{^} 9.44 (s, 1H), 8.72 (s, 1H), 8.20 (s, 1H), 7.47 (bs, 2H), 7.04 (d, J = 8.4 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 4.70 (q, J = 5.6 Hz, 1H), 3.19 (s, 3H), 2.49 (s, 3H), 1.66 (s, 3H), 1.55 (s, 3H), 1.49 (d, J = 5.6 Hz, 3H); LCMS m/z = 378 [M+H]⁺ Example 51: 3-(4-Amino-6-(1-methoxyethyl)-7-methyl-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-9-yl)-2,4-dimethylphenol (Isomer-I)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-(4-amino-6-(1-methoxyethyl)-7-methyl-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-9-yl)-2,4-dimethylphenol (Example 50) using 9-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-6-(2-methoxypropan-2- yl)-7-methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4-amine as a starting material.¹H NMR (DMSO-d₆) ^ 9.45 (s, 1H), 8.52 (s, 1H), 8.20 (s, 1H), 7.47 (bs, 2H), 7.04 (d, J = 8.4 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 2.95 (s, 3H), 2.67 (s, 3H), 1.66 (s, 9H), 1.57 (s, 3H); LCMS m/z = 392 [M+H]⁺ Example 53: 3-(4-Amino-6-(1-ethoxyethyl)-7-methyl-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-9-yl)-2,4-dimethylphenol (Isomer-I)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-(4-amino-6-(1-methoxyethyl)-7-methyl-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-9-yl)-2,4-dimethylphenol (Example 50) using 6-(1-ethoxyethyl)-9-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-7- methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4-amine (Isomer-I)as a starting material. ¹H NMR (DMSO-d₆) ^ 9.44 (s, 1H), 8.52 (s, 1H), 8.20 (s, 1H), 7.50 (bs, 2H), 7.04 (d, J = 8.4 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 2.95 (s, 3H), 2.67 (s, 3H), 1.66 (m, 9H), 1.57 (s, 3H); LCMS m/z = 392 [M+H]⁺ Example 54: 3-(4-Amino-6-(1-ethoxyethyl)-7-methyl-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-9-yl)-2,4-dimethylphenol (Isomer-II)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-(4-amino-6-(1-methoxyethyl)-7-methyl-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-9-yl)-2,4-dimethylphenol (Example 50) using 6-(1-ethoxyethyl)-9-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-7- methyl-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4-amine (Isomer-II) as a starting material.¹H NMR (DMSO-d6) ^{^} 9.44 (s, 1H), 8.73 (s, 1H), 8.20 (s, 1H), 7.47 (bs, 2H), 7.04 (d, J = 8.4 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 4.79 (m, 1H), 3.43 (m, 2H), 2.49 (s, 3H), 1.66 (s, 3H), 1.55 (s, 3H), 1.49 (m, 3H), 1.14 (m, 3H); LCMS m/z = 392 [M+H]⁺ Example 55: 3-(4-Amino-7-methyl-6-(1-propoxyethyl)-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-9-yl)-2,4-dimethylphenol (Isomer-I)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-(4-amino-6-(1-methoxyethyl)-7-methyl-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-9-yl)-2,4-dimethylphenol (Example 50) using 9-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-7-methyl-6-(1- propoxyethyl)-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4-amine (Isomer-I) as a starting material.¹H NMR (DMSO-d₆) ^ 9.44 (s, 1H), 8.72 (s, 1H), 8.20 (s, 1H), 7.45 (bs, 2H), 7.04 (d, J = 8.4 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 4.78 (m, 1H), 3.28 (m, 2H), 2.49 (s, 3H), 1.65 (s, 3H), 1.56 (s, 3H), 1.49 (m, 6H), 0.87 (t, J = 7.6 Hz, 3H); LCMS m/z = 406 [M+H]⁺ Example 56: 3-(4-Amino-7-methyl-6-(1-propoxyethyl)-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-9-yl)-2,4-dimethylphenol (Isomer-II)

The title compound was prepared by following the same reaction protocol as described in the synthesis of 3-(4-amino-6-(1-methoxyethyl)-7-methyl-9H- pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-9-yl)-2,4-dimethylphenol (Example 50) using 9-(3-((4-methoxybenzyl)oxy)-2,6-dimethylphenyl)-7-methyl-6-(1- propoxyethyl)-9H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-4-amine (Isomer-II) as a starting material.¹H NMR (DMSO-d₆) ^ 9.44 (s, 1H), 8.72 (s, 1H), 8.20 (s, 1H), 7.45 (bs, 2H), 7.04 (d, J = 8.4 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 4.78 (m, 1H), 3.28 (m, 2H), 2.49 (s, 3H), 1.65 (s, 3H), 1.56 (s, 3H), 1.49 (m, 6H), 0.87 (t, J = 7.6 Hz, 3H); LCMS m/z = 406 [M+H]⁺ The racemic mixture of atropisomers was separated using chiral supercritical fluid chromatography (SFC) method. The appropriate fractions for each peak were combined, concentrated and usually taken in a mixture of water and a suitable miscible organic solvent such as ethanol, isopropyl alcohol, acetonitrile or a mixture thereof and freeze-dried. The separated products were reanalyzed by chiral SFC to assess chiral purity. Table 5: Analytic data of racemic mixtures of atropisomers of compounds of Formula (I)

Exemplary separated atropisomers and their spectral data are shown in Table 6 as below. Table 6: Separated Atropisomers of compounds of Formula (I) with spectral data

Abbreviations: AcOH = acetic acid °C = degree Celsius DEA = Diethylamine DMF = N,N-dimethylformamide EtOAc = ethyl acetate EtOH = ethanol h = hour(s) IPA = 2-propanol LCMS = Liquid chromatography-mass spectrometry MeOH = methanol mg = milligram ml = milliliter min = minute(s) MTBE = methyl tert-butyl ether m/z = mass to charge ratio NBS = N-bromosuccinimide ¹H NMR = Proton nuclear magnetic resonance -OPMB = 4-methoxybenzyloxy PdCl2dppf .CH2Cl2 = [1,1′Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane Pd₂dba₃ = Tris(dibenzylideneacetone)dipalladium(0) r.t. = room temperature THF = tetrahydrofuran Xantphos = 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene PHARMACOLOGICAL ACTIVITY: PKMYT1 biochemical assay Inhibition of human PKMYT1 (Thermo Scientific # A30984) enzyme activity by compounds was measured using ADP-Glo^TM assay (Promega (# V9101)). Compounds, enzyme, and ATP were diluted in reaction buffer containing 70mM HEPES, 3mM MgCl₂, 3mM MnCl₂, Phosphatase inhibitor and 1.2mM DTT.1.66 µl of recombinant human PKMYT-1 protein (final concentration 100 nM) was incubated with 1.66 µl test compound or DMSO control prepared in reaction buffer. This compound and enzyme mixture was incubated at room temperature for 15 minutes. Post incubation, 1.66 µl of ATP was added at a final concentration of 10 µM. Reaction mixture was incubated for 1 hour at 30°C with shaking.5 µl of ADP- Glo reagent was then added and incubated further in the dark for 30 minutes.10 µl of KINASE Glo detection reagent was added to reaction mixture and incubated for 30 minutes at room temperature. Luminescence counts were measured using Victor Nivo Multimode plate reader (PerkinElmer) with 1000 ms integration time. Calculation % Inhibition = 100 - ((RLU in compound treated well-Blank)/ (RLU in DMSO well-Blank)*100). Table 7: Inhibition of human PKMYT1 enzyme activity by compounds of Formula (I) % inhibition @ 100 nM: > 70% = ***; 50-70% = **; < 50% = *

Table 8: Inhibition of human PKMYT1 enzyme activity by Atropisomers of compounds of Formula (I) % inhibition @ 100 nM: > 70% = ***; 50-70% = **; < 50% = * IC50: < 20 nM = ***; 20-100 nM = **; 100-1000 nM = *

Claims

We claim: 1. A compound of Formula (I)

wherein, ring A is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- 5 to 6 membered heteroaryl, substituted- or unsubstituted- 5 to 8 membered carbocycle, and substituted- or unsubstituted- 5 to 8 membered heterocycle; X and Y are independently selected from -N or -CR⁶; R¹ and R² are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- heteroaryl, alkenyl, -NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, - C(=O)N(R^7b)₂, and -N(R^7b)₂, or R¹ and R² together can form a substituted- or unsubstituted- 5-8 membered heterocycle; R³ and R⁴ are independently selected from cyano, substituted- or unsubstituted- heteroaryl, -NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, - C(=O)N(R^7b)2, and -N(R^7b)2, or R³ and R⁴ together can form a substituted- or unsubstituted- 5-8 membered heterocycle, or substituted- or unsubstituted- 5-6 membered heteroaryl; R⁵ is selected from hydrogen, hydroxy, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, - NR^7bC(=O)R^7a, -OR^7b, - C(=O)OR^7b, -C(=O)N(R^7b)2, and -N(R^7b)2; R⁶ is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle and - N(R^7b)₂; R^7a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, and substituted- or unsubstituted- heterocycle; R^7b is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, and substituted- or unsubstituted- heterocycle; n is an integer selected from 1-5; and when R¹ and R² together is not a substituted- or unsubstituted- 5-8 membered heterocycle and R³ and R⁴ together is not a substituted- or unsubstituted- 5-8 membered heterocycle or substituted- or unsubstituted- 5-6 membered heteroaryl, then n is 2 or >2, and R^7b is hydrogen when -OR^7b is part of R⁵; or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof.

2. The compound of claim 1, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein ring A is selected from substituted- or unsubstituted- aryl or substituted- or unsubstituted- 5 to 6 membered heteroaryl.

3. The compound of claim 1, which is a compound of Formula (IA) represented by the structure:

wherein, ring A is phenyl; X is N, Y is -CH-; R¹ and R² are methyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-8 membered heterocycle, or substituted- or unsubstituted- 5-6 membered heteroaryl; and R⁵ and n are each the same as defined in claim 1; or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof.

4. The compound of claim 1, which is a compound of Formula (IA) represented by the structure:

wherein, ring A is phenyl; X is N, Y is -CH-; R¹ is methyl; R² is cycloalkyl or heterocycle or heteroaryl or OR^7b, wherein R^7b alkyl or cycloalkyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-6 membered heteroaryl; and R⁵ and n are each the same as defined in claim 1; or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof.

5. The compound of claim 1, which is a compound of Formula (IA) represented by the structure:

wherein, ring A is phenyl; X is N, Y is -CH-; R¹ is cycloalkyl or heterocycle or OR^7b, wherein R^7b is alkyl or cycloalkyl; R² is methyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-6 membered heteroaryl; and R⁵ and n are each the same as defined in claim 1; or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof.

6. The compound of claim 1, which is a compound of Formula (IA) represented by the structure:

wherein, ring A is phenyl; X is N, Y is -CH-; R¹ is methyl; R² is substituted alkyl, wherein substituent is -OR^8b; R^8b is selected from hydrogen, alkyl, haloalkyl, and cycloalkyl; R³ and R⁴ together can form a substituted- or unsubstituted- 5-6 membered heteroaryl; and R⁵ and n are each the same as defined in claim 1; or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof.

7. The compound of claim 1, which is a compound of Formula (IB) represented by the structure:

wherein, ring A is phenyl; X is N, Y is -CH-; R¹ and R² are methyl; R³ is -C(=O)N(R^7b)2, and R⁴ is -N(R^7b)2, wherein R^7b is hydrogen; and R⁵ and n are each the same as defined in claim 1; or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof.

8. The compound of claim 1, which is a compound of Formula (IC) and Formula (ID) represented by the structure:

wherein Y is N or CR⁶; R¹ and R² are independently hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- heteroaryl, alkenyl, -NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, -C(=O)N(R^7b)2, or -N(R^7b)₂; R^5a is C1-4-alkyl or halogen; R^5b is hydrogen, C1-4-alkyl, or halogen; R^5c is hydroxy; R^5d is hydrogen or hydroxy; R⁶ is hydrogen, halogen, or C1-4-alkyl; R^7a is substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, or substituted- or unsubstituted- heterocycle; and R^7b is hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, or substituted- or unsubstituted- heterocycle; or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof.

9. The compound of claim 8, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein Y is CR⁶; R¹ and R² are independently hydrogen; halogen; nitro; cyano; C_1-4-alkyl optionally substituted with one or more groups selected from the group consisting of halogen, -O-R^8b, -N(H)R⁸, -N(alkyl)R⁸, C_3-6-cycloalkyl, and heterocycle, in which said C_3-6-cycloalkyl and heterocycle may be further substituted with one or more groups selected from the group consisting of halogen, cyano, C1-4-alkyl, -O-R^8b, C1-4-haloalkyl, -N(H)R⁸, and - N(alkyl)R⁸; C_3-6-cycloalkyl optionally substituted with one or more groups selected from the group consisting of halogen, cyano, C1-4-alkyl, -O-R^8b, C1- 4-haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; heterocycle optionally substituted with one or more groups selected from the group consisting of halogen, cyano, -O-R^8b, C_1-4-alkyl, -CH₂-OR^8b, C_1-4-haloalkyl, -N(H)R⁸, and - N(alkyl)R⁸; heteroaryl optionally substituted with one or more groups selected from the group consisting of halogen, cyano, C1-4-alkyl, -O-(C1-4- alkyl), C_1-4-haloalkyl, -O-(C_1-4-haloalkyl), -N(alkyl)alkyl, -N(H)alkyl, and -NH2; C2-4 alkenyl; -OR^7b; or -N(R^7b)2; R^7b is hydrogen; C3-6-cycloalkyl; or C1-4-alkyl optionally substituted with one or more groups selected from the group consisting of halogen and C_3-6- cycloalkyl; R⁸ is hydrogen, C1-4-alkyl, or C3-6-cycloalkyl; and R^8b is hydrogen, C1-4-alkyl, C1-4-haloalkyl, or C3-6-cycloalkyl.

10. The compound of claim 9, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein R¹ and R² are independently hydrogen; halogen; nitro; cyano; C_1-4-alkyl optionally substituted with one or more groups selected from the group consisting of halogen, -O-R^8b, -N(H)R⁸, -N(alkyl)R⁸, C_3-6-cycloalkyl, piperidinyl, pyrrolidinyl, and morpholinyl, in which said C_3-6-cycloalkyl, piperidinyl, pyrrolidinyl, and morpholinyl may be further substituted with one or more groups selected from the group consisting of halogen, cyano, - O-R^8b, C_1-4-alkyl, C_1-4-haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; C_3-6-cycloalkyl optionally substituted with one or more groups selected from the group consisting of halogen, cyano, -O-R^8b, C1-4-alkyl, C1-4-haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; piperidinyl, pyrrolidinyl, morpholinyl, or 6- azaspiro[2.5]octyl, each of which may be substituted with one or more groups selected from the group consisting of halogen, cyano, -O-R^8b, C1-4- alkyl, -CH2-OR^8b, C1-4-haloalkyl, -N(H)R⁸, and -N(alkyl)R⁸; pyrazolyl optionally substituted with one or more groups selected from the group consisting of halogen, cyano, C1-4-alkyl, -O-(C1-4-alkyl), C1-4-haloalkyl, -O- (C1-4-haloalkyl), -N(alkyl)alkyl, -N(H)alkyl, and -NH2; C2-4 alkenyl; -OR^7b; or -N(R^7b)₂; R^7b is hydrogen; C3-6-cycloalkyl; or C1-4-alkyl optionally substituted with one or more groups selected from the group consisting of halogen and C3-6- cycloalkyl; R⁸ is hydrogen, C1-4-alkyl, or C3-6-cycloalkyl; and R^8b is hydrogen, C1-4-alkyl, C1-4-haloalkyl, or C3-6-cycloalkyl.

11. The compound of claim 1, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, wherein the compounds are selected from the group consisting of:

12. A process for preparing heteroaryl compounds of Formula (I)

wherein, ring A is selected from substituted- or unsubstituted- aryl, substituted- or unsubstituted- 5 to 6 membered heteroaryl, substituted- or unsubstituted- 5 to 8 membered carbocycle, and substituted- or unsubstituted- 5 to 8 membered heterocycle; X and Y are independently selected from -N or -CR⁶; R¹ and R² are independently selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, substituted- or unsubstituted- heteroaryl, alkenyl, -NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, - C(=O)N(R^7b)₂, and -N(R^7b)₂, or R¹ and R² together can form a substituted- or unsubstituted- 5-8 membered heterocycle; R³ and R⁴ are independently selected from cyano, substituted- or unsubstituted- heteroaryl, -NR^7bC(=O)R^7a, -OR^7b, -C(=O)OR^7b, - C(=O)N(R^7b)2, and -N(R^7b)2, or R³ and R⁴ together can form a substituted- or unsubstituted- 5-8 membered heterocycle, or substituted- or unsubstituted- 5-6 membered heteroaryl; R⁵ is selected from hydrogen, hydroxy, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle, - NR^7bC(=O)R^7a, -OR^7b, - C(=O)OR^7b, -C(=O)N(R^7b)2, and -N(R^7b)2; R⁶ is selected from hydrogen, halogen, nitro, cyano, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, substituted- or unsubstituted- heterocycle and - N(R^7b)2; R^7a is selected from substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, and substituted- or unsubstituted- heterocycle; R^7b is selected from hydrogen, substituted- or unsubstituted- alkyl, substituted- or unsubstituted- cycloalkyl, and substituted- or unsubstituted- heterocycle; R^8b is selected from hydrogen, alkyl, haloalkyl, and cycloalkyl; n is an integer selected from 1-5; and when R¹ and R² together is not a substituted- or unsubstituted- 5-8 membered heterocycle and R³ and R⁴ together is not a substituted- or unsubstituted- 5-8 membered heterocycle or substituted- or unsubstituted- 5-6 membered heteroaryl, then n is 2 or >2, and R^7b is hydrogen when -OR^7b is part of R⁵; or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof comprising the steps of: i) treating starting compound (a)

with compound (d)

in presence of a base, a catalyst and a solvent to obtain compound (b);

iii) treating the compound (c) of step (ii) with a reagent to obtain heteroaryl compounds of Formula (I) or heterocycles; and iv) optionally, subjecting compound (c) of step (ii) to deprotection of protecting group to obtain the compounds of Formula (I); wherein the compounds of Formula (I) are compounds of Formula (IA) or compounds of Formula (IB) or compounds of Formula (IC) or compounds of Formula (ID).

13. The process as claimed in claim 12, wherein the base in step (i) is selected from a group comprising of sodium carbonate, caesium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, ammonium hydroxide, potassium carbonate, potassium bicarbonate and magnesium carbonate.

14. The process as claimed in claim 13, wherein the base is caesium carbonate.

15. The process as claimed in claim 12, wherein the catalyst in step (i) is selected from the group comprising of Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis (triphenylphosphine)palladium(0) and tris(dibenzylideneacetone) dipalladium(0).

16. The process as claimed in claim 15, wherein the catalyst is Tris(dibenzylideneacetone)dipalladium(0).

17. The process as claimed in claim 12, wherein the solvent in step (i) is selected from the group comprising of diethyl ether, dimethylformamide tetrahydrofuran, dichloromethane, methanol, DMSO, dimethoxy ethane, dimethoxy methane, dibutyl ether, ethanol, isopropyl alcohol, acetonitrile and diisopropyl ether.

18. The process as claimed in claim 17, wherein the solvent is 1,2-dimethoxy ethane.

19. The process as claimed in claim 12, wherein the nitrile in step (ii) is selected from a group comprising of malononitrile, propionitrile and ethanenitrile, benzonitrile.

20. The process as claimed in claim 19, wherein the nitrile is malononitrile.

21. The process as claimed in claim 12, wherein the base in step (ii) is selected from a group comprising of sodium tertiary butoxide, sodium hydride, lithium hydride, ammonium hydroxide, potassium hydride, rubidium hydride, caesium hydride or lithium aluminium hydride.

22. The process as claimed in claim 21, wherein the base is sodium tertiary butoxide, sodium bicarbonate, or sodium hydride.

23. The process as claimed in claim 12, wherein the catalyst in step (ii) is selected from a group comprising Bis(diphenylphosphino)ferrocene]dichloropalladium(II), Palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0) and tris(dibenzylideneacetone)dipalladium(0).

24. The process as claimed in claim 23, wherein the catalyst is Bis(diphenylphosphino)ferrocene]dichloropalladium(II).

25. The process as claimed in claim 12, wherein the solvent in step (ii) is selected from a group comprising of DMSO, 1,2-dimethoxy ethane, methanol, dichloromethane, toluene, dimethylformamide, tetrahydrofuran, diethyl ether and chlorinated solvent.

26. The process as claimed in claim 25, wherein the solvent is 1,2-dimethoxy ethane.

27. The process as claimed in claim 12, wherein the reagent in step (iii) is selected from a group comprising of formamide, ethyl acetate, ethyl carbonate and guanidine hydrochloride.

28. A pharmaceutical composition comprising a compound of any one of claims 1 to 11, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof, and a pharmaceutically acceptable excipient or carrier.

29. Use of a compound of any one of claims 1 to 11, or a pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof for manufacturing a medicament for a treatment of a cancer associated with PKMYT1 protein.

30. Use of a compound of any one of claims 1 to 11, or a pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof for a treatment of a cancer associated with PKMYT1 protein.

31. A compound of any one of claims 1 to 11, or a pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof for a treatment of a cancer associated with PKMYT1 protein.

32. A method of inhibiting PKMYT1 protein comprising administering to a subject therapeutically effective amount of a pharmaceutical composition comprising at least one of the compounds of any one of claims 1 to 11, or pharmaceutically acceptable salts, solvates, polymorphs, tautomers, atropisomers, optical and geometric isomers, prodrugs, or deuterated compounds including isotopes thereof.

33. The method as claimed in claim 32 for treatment of cancer associated with PKMYT1 protein.

34. The method of claim 32 or 33, wherein the subject has cancer.

35. The method of claim 32, wherein the cancer depends on the activity of PKMYT1.

36. The method of any one of claims 32 or 33, wherein the cancer overexpresses CCNE1.

37. The method of any one of claims 32 to 34, wherein the cancer has an inactivating mutation in the FBXW7 and PPP2R1A genes.

38. The method of any one of claims 32 to 35, wherein the cancer is a solid tumor.

39. The method of any one of claims 32 to 35, wherein the cancer is breast cancer, colorectal cancer, endometrial cancer, esophageal cancer, glioblastoma, hepatocellular carcinoma, lung cancer, neuroblastoma, ovarian cancer, prostate cancer, stomach cancer, or uterine cancer.