+

US20080132699A1 - Process For the Preparation of Diazine Derivatives - Google Patents

Process For the Preparation of Diazine Derivatives Download PDF

Info

Publication number
US20080132699A1
US20080132699A1 US10/592,820 US59282005A US2008132699A1 US 20080132699 A1 US20080132699 A1 US 20080132699A1 US 59282005 A US59282005 A US 59282005A US 2008132699 A1 US2008132699 A1 US 2008132699A1
Authority
US
United States
Prior art keywords
formula
mmol
preparation
process according
triazol
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10/592,820
Other languages
English (en)
Inventor
Markus Ege
Wolfgang Jenni
Thomas von Hirschheydt
Edgar Voss
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hoffmann La Roche Inc
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=34924554&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20080132699(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Individual filed Critical Individual
Assigned to F. HOFFMANN-LA ROCHE AG reassignment F. HOFFMANN-LA ROCHE AG ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: JENNI, WOLFGANG, EGE, MARKUS, VON HIRSCHHEYDT, THOMAS, VOSS, EDGAR
Assigned to HOFFMANN-LA ROCHE, INC. reassignment HOFFMANN-LA ROCHE, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: F. HOFFMANN-LA ROCHE AG
Publication of US20080132699A1 publication Critical patent/US20080132699A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the invention relates to a new process for the preparation of diazine derivatives of formula I:
  • cycloalkyl means a monocyclic saturated hydrocarbon ring with 3 to 7, preferably 3 to 6, ring atoms.
  • saturated carbocyclic groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.
  • heterocyclyl means a saturated, monocyclic ring with 5 to 6 ring atoms which contains up to 3, preferably 1 or 2 heteroatoms selected independently from N, O or S and the remaining ring atoms being carbon atoms.
  • Such saturated heterocyclic group can be optionally substituted one to three, preferably one or two times by alkyl, which is defined as above, preferably by methyl.
  • alkyl which is defined as above, preferably by methyl.
  • Examples of such saturated heterocyclic groups are pyrrolidinyl, morpholinyl, piperazinyl, N-methyl-piperazinyl, piperidyl and the like.
  • aryl means a mono- or bicyclic aromatic ring with 6 to 10 ring carbon atoms.
  • aryl groups are phenyl and naphthyl, preferably phenyl.
  • Such aryl groups are optionally substituted one to three, preferably one to two times by halogen, amino, hydroxy, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, halogenated (C 1 -C 4 )alkyl or halogenated (C 1 -C 4 )alkoxy.
  • heteroaryl means a mono- or bicyclic aromatic ring with 5 to 10, preferably 5 to 6, ring atoms, which contains up to 3, preferably 1 or 2 heteroatoms selected independently from N, O or S and the remaining ring atoms being carbon atoms.
  • heteroaryl groups are e.g.
  • heteroaryl groups are optionally substituted one to two times, preferably one time, by (C 1 -C 4 )alkyl.
  • alkyl as used herein means a saturated, straight-chain or branched-chain hydrocarbon containing from 1 to 6, preferably 1 to 4, carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl, t-butyl, n-pentyl, n-hexyl.
  • alkoxy as used herein means an alkyl-O— group wherein the alkyl is defined as above.
  • halogenated alkyl as used herein means an alkyl group as defined above which is substituted one or several times, preferably one to six and especially one to three times, by halogen, preferably by fluorine or chlorine, especially by fluorine. Examples are difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, perfluoroethyl, and the like, especially trifluoromethyl.
  • halogenated alkoxy means an alkoxy group as defined above which is substituted one or several times by halogen, preferably by fluorine or chlorine, especially fluorine. Examples are difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, perfluoroethoxy and the like, especially trifluoromethoxy.
  • halogen means fluorine, chlorine, bromine and iodine, preferably fluorine, chlorine or bromine and especially fluorine and chlorine.
  • X, ring A, W and R 1 have the significance given above and Y is iodine or bromine and not both X and Y are bromine.
  • the synthesis of the compounds of formula I starts from the corresponding dihalodiazines of formula III.
  • the preparation of these dihalodiazines of formula III is described in the accompanying examples or in e.g. WO 2004/000811, Pieterse, K., et al., Chemistry-A European Journal 9 (2003) 5597-5604 and Sato, N., J. Heterocyclic Chem., 19 (1982) 673-674, Draper, T. L., et al., J. Org. Chem. 60 (1995) 748-50; Goodman, A.
  • Step 1 the dihalodiazines of formula III are reacted with alkyne derivatives of formula IV in a Sonogashira cross-coupling reaction in the presence of catalytic amounts of copper iodide and a palladium complex, e.g. Pd(PPh 3 ) 4 , Pd(PPh 3 ) 2 Cl 2 or the like.
  • the reaction is carried out in the presence of a base like triethyl amine, diisopropyl amine, isopropyl amine, piperidine, morpholine or pyrrolidine and in solvents like tetrahydrofuran, N,N-dimethylformamide or mixtures thereof at temperatures varying from 20° C. to 120° C. yielding derivatives of formula V.
  • the compounds of formula I wherein W is —HC ⁇ CH— are obtained.
  • Such compounds are named I-a.
  • a catalytic hydrogenation is performed.
  • the catalysts are usually used as finely dispersed solids or adsorbed on to an inert support such as charcoal (C), calcium carbonate (CaCO 3 ), barium sulfate (BaSO 4 ) or alumina (Al).
  • Typical catalyst are e.g.
  • Pd/Pb/CaCO 3 Pd—CaCO 3 —PbO system wherein the PbO acts as catalytic poison and tempers the reactivity
  • Pd/CaCO 3 Pd/BaSO 4 or Pt/BaSO 4 eventually poisoned with quinoline, especially Pd/CaCO 3 or Pd/Pb/CaCO 3
  • nickel boride(Ni 2 B) can be used as catalyst.
  • the mol % of catalyst added can vary between 1 mol % and 50 mol %, preferably between 5 and 25 mol %.
  • a catalytic poison like can be used to slow down the reaction and to prevent further hydrogenation according to Step 3.
  • the reaction is typically carried out at temperatures between 0° C.
  • the compounds of formula I wherein W is —CH 2 —CH 2 — are obtained.
  • Such compounds are named I-b.
  • Typical catalysts are e.g. Pt, PtO 2 , Pd, Rh, Ru and Ni (late transition metals)—usually used as finely dispersed solids or adsorbed on to an inert support such as charcoal (C), calcium carbonate (CaCO 3 ) or alumina (Al).
  • Pd/C, Pd/CaCO 3 or PtO 2 is used.
  • the mol % of catalyst added can vary between 1 mol % and 50 mol %, preferably between 5 and 25 mol %.
  • the reaction is typically carried out at temperatures between 0° C. and 50° C., at hydrogen pressures between 1 ⁇ 10 3 and 4 ⁇ 15 Pa, preferably between 2 ⁇ 10 3 and 15 ⁇ 10 4 Pa, in solvents like methanol, ethanol, tetrahydrofuran, acetone, ethyl acetate or mixtures thereof.
  • solvents like methanol, ethanol, tetrahydrofuran, acetone, ethyl acetate or mixtures thereof.
  • a variety of homogeneous catalysts are also effective e.g. Wilkinson's catalyst [(PPh 3 ) 3 RhCl].
  • step 4 of scheme 1 the compounds of formula I-a are converted to the compounds of formula I-b by obtained by a reduction reaction.
  • a catalytic hydrogenation is performed.
  • Typical catalysts are e.g. Pt, PtO 2 , Pd, Rh, Ru and Ni (late transition metals)—usually used as finely dispersed solids or adsorbed on to an inert support such as charcoal (C), calcium carbonate (CaCO 3 ) or alumina (Al).
  • Pd/C, Pd/CaCO 3 or PtO 2 is used.
  • the mol % of catalyst added can vary between 1 mol % and 50 mol %, preferably between 5 and 25 mol %.
  • the reaction is typically carried out at temperatures between 0° C. and 50° C., at hydrogen pressures between 1 ⁇ 10 3 and 4 ⁇ 10 5 Pa, preferably between 2 ⁇ 10 3 and 15 ⁇ 10 4 Pa, in solvents like methanol, ethanol, tetrahydrofuran, acetone, ethyl acetate or mixtures thereof.
  • solvents like methanol, ethanol, tetrahydrofuran, acetone, ethyl acetate or mixtures thereof.
  • homogeneous catalysts are also effective e.g. Wilkinson's catalyst [(PPh 3 ) 3 RhCl].
  • An embodiment of the invention is a process according to Step 2 or Step 3 of Scheme 1, for the preparation of diazine derivatives of formula I
  • Another embodiment of the invention is a process according to Step 2 of Scheme 1, for the preparation of diazine derivatives of formula I-a
  • Another embodiment of the invention is a process according to Step 3 of Scheme 1, for the preparation of diazine derivatives of formula I-b
  • Another embodiment of the invention is a process according to Step 4 of Scheme 1, for the preparation of diazine derivatives of formula I-b
  • Another embodiment of the invention is a process according to Scheme 1, for the preparation of diazine derivatives of formula I, wherein
  • X is chlorine or bromine.
  • n is 1 to 4
  • Another embodiment of the invention is a process according to Scheme 1, for the preparation of diazine derivatives of formula I, wherein
  • X is chlorine or bromine.
  • n is 1 to 4 R 1 is heteroaryl.
  • Another embodiment of the invention is a process according to Scheme 1, for the preparation of diazine derivatives of formula I, wherein
  • R 1 is heteroaryl
  • Another embodiment of the invention is a process according to Scheme 1, for the preparation of diazine derivatives of formula I, wherein
  • W is —CH 2 —CH 2 —.
  • Another embodiment of the invention is a process according to Step 2b of Scheme 1, for the preparation of diazine derivatives of formula I, wherein
  • W is —CH 2 —CH 2 —.
  • Another embodiment of the invention is a process according to Scheme 1, for the preparation of diazine derivatives of formula I, wherein
  • W is —CH ⁇ CH—.
  • Another embodiment of the invention is a process according to Step 2a of Scheme 1, for the preparation of diazine derivatives of formula I, wherein
  • W is —CH ⁇ CH—.
  • Another embodiment of the invention is a process according to Scheme 1, for the preparation of diazine derivatives of formula I, wherein
  • W is —CH 2 —CH 2 —; and the catalyst in the hydrogenation step 2 is Pd/C or PtO 2 .
  • Another embodiment of the invention is a process according to Scheme 1 for the preparation of diazine derivatives of formula I, wherein
  • W is —CH 2 —CH 2 —
  • the catalyst in the hydrogenation step 2 is PtO 2 .
  • Another embodiment of the invention is a process according to Scheme 1 for the preparation of diazine derivatives of formula I, wherein
  • W is —CH 2 —CH 2 — or —CH ⁇ CH—
  • the catalyst in the hydrogenation step 2 is Pd/CaCO 3 .
  • Another embodiment of the invention is a process according to Scheme 1, for the preparation of diazine derivatives of formula I, wherein
  • W is —CH ⁇ CH—
  • the catalyst in the hydrogenation step is Pd/CaCO 3 or Pd/Pb/CaCO 3 .
  • Another embodiment of the invention is a process according to Scheme 1 for the preparation of diazine derivatives of formula I, wherein ring A is
  • Another embodiment of the invention is a process according to Scheme 1, for the preparation of diazine derivatives of formula I, wherein ring A is
  • Another embodiment of the invention is a process according to Scheme 1, for the preparation of diazine derivatives of formula I, wherein ring A is
  • Another embodiment of the invention is a process according to Scheme 1, for the preparation of diazine derivatives of formula I, wherein ring A is
  • 2-Pyrimidinol hydrochloride 13.26 g, 100 mmol is dissolved in 2N NaOH (50 ml) and bromine (17.98 g, 112.5 mmol) is added over 15 min. The mixture is stirred for 45 min at r.t. and then concentrated in vacuo to yield a brownish solid.
  • But-3-yn-1-ol (49.57 g, 707.2 mmol) and triethylamine (107.7 mL, 777 mmol, dried over KOH) are dissolved in dry dichloromethane (500 mL) under a nitrogen atmosphere and cooled to 0° C.
  • Methanesulfonyl chloride (54.8 mL, 708 mmol)
  • 500 mL of dry dichloromethane is added within 90 min while keeping the temperature below 5° C.
  • the mixture is stirred for 3.5 hours at room temperature, then poured onto 2.5 L of ice water.
  • the organic phase is separated and washed with 2 ⁇ 500 mL of water and 1 ⁇ 250 mL of brine and dried over sodium sulfate.
  • the volatiles are removed to yield 94.18 g of the methane sulfonate (631.2 mmol, 89.2%) as a yellow liquid.
  • a suspension of NaOH (37.86 g, 946.5 mmol), sodium iodide (94.65 g, 631.5 mmol) and 1H-[1,2,3]triazole (61.03 g, 883.6 mmol) in 2-methyl-2-butanol (750 mL) is refluxed for 1 h under an inert atmosphere. After cooling to room temperature the methane sulfonate (94.18 g, 631.2 mmol) is added within 5 minutes. The resulting suspension is then heated to reflux for 3 h, cooled to room temperature and concentrated in vacuo at 45° C.
  • 3-Chloro-6-(4-[1,2,3]triazol-1-yl-but-1-ynyl)-pyridazine (2.50 g, 10.7 mmol) is dissolved in ethyl acetate (450 ml) and hydrogenated at 3 ⁇ 10 3 Pa H 2 -pressure for 3.5 h at r.t. in the presence of palladium on charcoal (10%, 2.50 g). The reaction mixture is filtered and concentrated in vacuo.
  • 3-Chloro-6-(4-[1,2,3]triazol-1-yl-but-1-ynyl)-pyridazine (0.100 mg, 0.43 mmol) is dissolved in methanol (10 ml) and hydrogenated at 3 ⁇ 10 3 Pa H 2 -pressure for 4.5 h at r.t. in the presence of platinum(IV) oxide ⁇ H 2 O (0.044 mg, 0.18 mmol).
  • the reaction mixture is filtered and concentrated in vacuo to yield 3-chloro-6-(4-[1,2,3]triazol-1-yl-butyl)-pyridazine as a colorless solid. Yield 0.059 g (58%).
  • 2-Bromo-5-(4-[1,2,3]triazol-1-yl-but-1-enyl)-pyrazine (0.020 mg, 0.07 mmol) is dissolved in methanol (4 ml) and hydrogenated at 3 ⁇ 10 3 Pa H 2 -pressure for 1 h at r.t. in the presence of platinum(IV) oxide ⁇ H 2 O (0.007 mg, 0.03 mmol).
  • the reaction mixture is filtered and concentrated in vacuo to yield 2-bromo-5-(4-[1,2,3]triazol-1-yl-butyl)-pyrazine and 2-bromo-5-(4-[1,2,3]triazol-1-yl-butyl)-pyrazine at the ratio of 80:20.
  • the different halogen-diazine-alkyne derivatives were dissolved in the appropriate solvent and hydrogenated in the presence of a catalyst.
  • the reaction mixture is filtered and concentrated in vacuo to yield 5-bromo-2-(4-[1,2,3]triazol-1-yl-butyl)-pyrimidine as a colorless solid.
  • the used catalysts and reaction conditions (mol % catalyst, solvent, reaction temperature, reaction time) are listed in Table 1.
  • the ratios of the obtained alkenes (A) and alkanes (B) were detected by 1 H-NMR (400 MHz, CDCl 3 ). Where the main products were isolated the yield is given.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Catalysts (AREA)
US10/592,820 2004-04-02 2005-03-31 Process For the Preparation of Diazine Derivatives Abandoned US20080132699A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP04008130.9 2004-04-02
EP04008130 2004-04-02
PCT/EP2005/003346 WO2005097777A1 (fr) 2004-04-02 2005-03-31 Procede de preparation de derives de diazine

Publications (1)

Publication Number Publication Date
US20080132699A1 true US20080132699A1 (en) 2008-06-05

Family

ID=34924554

Family Applications (2)

Application Number Title Priority Date Filing Date
US10/592,820 Abandoned US20080132699A1 (en) 2004-04-02 2005-03-31 Process For the Preparation of Diazine Derivatives
US11/096,286 Expired - Fee Related US7179812B2 (en) 2004-04-02 2005-03-31 Diazine derivatives

Family Applications After (1)

Application Number Title Priority Date Filing Date
US11/096,286 Expired - Fee Related US7179812B2 (en) 2004-04-02 2005-03-31 Diazine derivatives

Country Status (12)

Country Link
US (2) US20080132699A1 (fr)
EP (2) EP1758897A1 (fr)
JP (2) JP2007530626A (fr)
KR (2) KR20060131958A (fr)
CN (2) CN1934106A (fr)
AR (1) AR048455A1 (fr)
AU (2) AU2005231936A1 (fr)
BR (2) BRPI0509360A (fr)
CA (2) CA2561206A1 (fr)
RU (2) RU2006138425A (fr)
TW (1) TW200602329A (fr)
WO (2) WO2005097777A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0413605D0 (en) 2004-06-17 2004-07-21 Addex Pharmaceuticals Sa Novel compounds
WO2010064134A2 (fr) * 2008-12-05 2010-06-10 Cadila Pharmaceuticals Ltd. Procédé de synthèse de la palipéridone
BR112019011211A2 (pt) 2016-12-16 2019-10-15 Basf Se compostos de fórmula i, composição, métodos para combater ou controlar pragas invertebradas, para proteger plantas em crescimento de ataque ou infestação por pragas invertebradas, semente, uso de um composto e método para tratar ou proteger um animal

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5681957A (en) * 1995-05-11 1997-10-28 Bayer Aktiengesellschaft Process for the preparation of substituted 2-fluoro-pyrimidines

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2952141B2 (ja) * 1993-01-08 1999-09-20 キヤノン株式会社 液晶性化合物、それを含む液晶組成物、及びこれを用いた液晶素子
EP0912562A1 (fr) 1996-07-19 1999-05-06 Takeda Chemical Industries, Ltd. Composes heterocycliques, leur production et leur utilisation
PE20011178A1 (es) 2000-04-07 2001-11-19 Takeda Chemical Industries Ltd Compuestos heterociclicos y su produccion
EP1310491A1 (fr) 2000-07-19 2003-05-14 Takeda Chemical Industries, Ltd. Procede de fabrication d'un derive de 1,2,3 triasol substitue en position 1
US6984653B2 (en) 2001-10-05 2006-01-10 Takeda Pharmaceutical Company Limited Heterocyclic compounds, oxazole derivatives, process for preparation of the same and use thereof
JP2003277379A (ja) * 2002-01-17 2003-10-02 Takeda Chem Ind Ltd 含窒素複素環化合物、その製造法および用途
WO2003059907A1 (fr) * 2002-01-17 2003-07-24 Takeda Chemical Industries, Ltd. Composes heterocycliques azotes : procede de preparation et d'utilisation
US7119203B2 (en) 2002-04-25 2006-10-10 Pharmacia Corporation Piperidinyl- and piperazinyl-sulfonylmethyl hydroxamic acids and their use as protease inhibitors

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5681957A (en) * 1995-05-11 1997-10-28 Bayer Aktiengesellschaft Process for the preparation of substituted 2-fluoro-pyrimidines

Also Published As

Publication number Publication date
AU2005231936A1 (en) 2005-10-20
JP2007530627A (ja) 2007-11-01
RU2006138424A (ru) 2008-05-10
WO2005097777A1 (fr) 2005-10-20
KR20060131958A (ko) 2006-12-20
WO2005097785A1 (fr) 2005-10-20
CA2561203A1 (fr) 2005-10-20
EP1737846A1 (fr) 2007-01-03
CA2561206A1 (fr) 2005-10-20
CN1934106A (zh) 2007-03-21
AU2005231937A1 (en) 2005-10-20
BRPI0509394A (pt) 2007-09-18
JP2007530626A (ja) 2007-11-01
EP1758897A1 (fr) 2007-03-07
CN1934102A (zh) 2007-03-21
AR048455A1 (es) 2006-04-26
BRPI0509360A (pt) 2007-09-11
KR100843533B1 (ko) 2008-07-03
KR20070006822A (ko) 2007-01-11
RU2006138425A (ru) 2008-06-20
US20050222228A1 (en) 2005-10-06
US7179812B2 (en) 2007-02-20
TW200602329A (en) 2006-01-16

Similar Documents

Publication Publication Date Title
TWI496781B (zh) 製備｛４，６－二胺基－２－［１－（２－氟苯甲基）－１Ｈ－吡唑并［３，４－ｂ］吡啶－３－基］嘧啶－５－基｝甲基胺基甲酸甲酯之方法及其使用作為醫藥活性化合物之純化
JP5189074B2 (ja) ドーパミンｄ３受容体のモジュレーターとしてのアザビシクロ［３．１．０］ヘキシル誘導体
TWI385147B (zh) 化學方法
EP2205562B1 (fr) Dérivés de 1,1,1-trifluoro-2-hydroxy-3-phénylpropane
WO2017118277A1 (fr) Forme cristalline d'un inhibiteur de la tyrosine kinase de bruton (btk) et son procédé de préparation
JP5394487B2 (ja) アミノテトラヒドロインダゾロ酢酸
EP0677046B1 (fr) Derives de piperazine utilises comme antagonistes de 5-ht
EP4206197A1 (fr) Procédé de préparation d'un nouvel inhibiteur de protéine kinase liée à rho et d'un intermédiaire dans le procédé de préparation
EP1458385A2 (fr) Imidazoles substitues par heteroaryle modulateurs du recepteur metabotropique du glutamate de type 5
CN103827101A (zh) 新的双环二氢喹啉-2-酮衍生物
US20200223840A1 (en) Substituted pyrrolidine amides iii
SG182784A1 (en) Processes of synthesizing dihydropyridophthalazinone derivatives
CN102015682B (zh) 作为肾素抑制剂的3,4-取代的哌啶衍生物
KR20130113352A (ko) 피페리딘 유도체 및 대사 장애의 치료를 위한 이의 용도
JP2006517218A (ja) アリールアルキルカルバメート誘導体の製造およびそれらの治療用途
EA016654B1 (ru) Пиперидиниламинопиридазины и их применение в качестве быстро диссоциирующих антагонистов рецептора допамина 2
US10252994B2 (en) Transition metal-catalyzed protocarboxylation of α-halo-acrylic acid derivatives
US20080132699A1 (en) Process For the Preparation of Diazine Derivatives
KR20090074179A (ko) Ｐｐａｒ 조절제로서 유용한 １ｈ­인돌­２­카르복실산 유도체
US20130158040A1 (en) Diazaindole inhibitors of crac
EP2760843A2 (fr) Antagonistes du nr2b sélectifs
WO2005037802A1 (fr) Derive de 5-arylpyrimidine
TW201041887A (en) 1H-pyrazolo[4,3-c]isoquinoline derivatives, their preparation and their application in therapeutics
US20170305915A1 (en) Indazole and indole derivatives as inhibitors of retinoic acid relates orphan receptor gamma (ror gamma) for the treatment of immune-related diseases
US5821245A (en) Use of naphthalene derivatives in treating lung carcinoma

Legal Events

Date Code Title Description
AS Assignment

Owner name: F. HOFFMANN-LA ROCHE AG, SWITZERLAND

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:EGE, MARKUS;JENNI, WOLFGANG;VON HIRSCHHEYDT, THOMAS;AND OTHERS;REEL/FRAME:020696/0366;SIGNING DATES FROM 20060713 TO 20060726

Owner name: HOFFMANN-LA ROCHE, INC., NEW JERSEY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:F. HOFFMANN-LA ROCHE AG;REEL/FRAME:020701/0355

Effective date: 20060810

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO PAY ISSUE FEE

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载