WO2012034065A1 - Intermédiaires d'aliskirène et procédé destiné à analyser la pureté de l'aliskirène - Google Patents
Intermédiaires d'aliskirène et procédé destiné à analyser la pureté de l'aliskirène Download PDFInfo
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- WO2012034065A1 WO2012034065A1 PCT/US2011/051076 US2011051076W WO2012034065A1 WO 2012034065 A1 WO2012034065 A1 WO 2012034065A1 US 2011051076 W US2011051076 W US 2011051076W WO 2012034065 A1 WO2012034065 A1 WO 2012034065A1
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- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000538 analytical sample Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 159000000009 barium salts Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000007905 drug manufacturing Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000005462 imide group Chemical group 0.000 description 1
- 238000010965 in-process control Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000000622 liquid--liquid extraction Methods 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000002461 renin inhibitor Substances 0.000 description 1
- 229940086526 renin-inhibitors Drugs 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000011863 silicon-based powder Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000000279 solid-state nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940058889 tekturna Drugs 0.000 description 1
- OKPJBCVKXMMXTJ-UHFFFAOYSA-N tert-butyl N-[8-[(3-amino-2,2-dimethyl-3-oxopropyl)carbamoyl]-6-hydroxy-3-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-2,9-dimethyldecan-5-yl]carbamate Chemical compound COCCCOC1=CC(CC(CC(NC(=O)OC(C)(C)C)C(O)CC(C(C)C)C(=O)NCC(C)(C)C(N)=O)C(C)C)=CC=C1OC OKPJBCVKXMMXTJ-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
- C07C247/02—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton
- C07C247/12—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
- C07C279/14—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
Definitions
- Figure 10 provides a H NMR spectrum of compound IX.
- a crystal form may be referred to herein as being characterized by graphical data "as depicted in" a Figure.
- Such data include, for example, powder X-ray diffracto- grams, FTIR spectra, and solid state NMR spectra.
- the skilled person will understand that such graphical representations of data may be subject to small variations, e.g., in peak relative intensities and peak positions due to factors such as variations in instrument response and variations in sample concentration and purity, which are well known to the skilled person. Nonetheless, the skilled person would readily be capable of comparing the graphical data in the Figures herein with graphical data generated for an unknown crystal form and confirming whether the two sets of graphical data are characterizing the same crystal form or two different crystal forms.
- Compound DC can be in amorphous or crystalline form.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Cette invention concerne des impuretés et des intermédiaires d'aliskirène, et des procédés pour les préparer. Cette invention concerne également des procédés de préparation d'aliskirène à l'aide de ces intermédiaires et de ces impuretés. Ces impuretés peuvent également être utilisées comme marqueurs ou étalons de référence pour déterminer la pureté de l'aliskirène ou de ses intermédiaires.
Applications Claiming Priority (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38133710P | 2010-09-09 | 2010-09-09 | |
| US61/381,337 | 2010-09-09 | ||
| US41406110P | 2010-11-16 | 2010-11-16 | |
| US61/414,061 | 2010-11-16 | ||
| US41997610P | 2010-12-06 | 2010-12-06 | |
| US61/419,976 | 2010-12-06 | ||
| US201161467126P | 2011-03-24 | 2011-03-24 | |
| US61/467,126 | 2011-03-24 | ||
| US201161474040P | 2011-04-11 | 2011-04-11 | |
| US61/474,040 | 2011-04-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2012034065A1 true WO2012034065A1 (fr) | 2012-03-15 |
Family
ID=44678048
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2011/051076 WO2012034065A1 (fr) | 2010-09-09 | 2011-09-09 | Intermédiaires d'aliskirène et procédé destiné à analyser la pureté de l'aliskirène |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2012034065A1 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105294612A (zh) * | 2014-06-05 | 2016-02-03 | 山东威智医药工业有限公司 | 阿利克仑中间体及其制备方法和应用 |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5559111A (en) | 1994-04-18 | 1996-09-24 | Ciba-Geigy Corporation | δ-amino-γ-hydroxy-ω-aryl-alkanoic acid amides |
| US5606078A (en) | 1994-04-18 | 1997-02-25 | Ciba-Geigy Corporation | 3,5-Disubstituted tetrahydrofuran-2-ones |
| US6333198B1 (en) | 1998-06-10 | 2001-12-25 | Glaxo Wellcome, Inc. | Compound and its use |
| WO2002008172A1 (fr) * | 2000-07-25 | 2002-01-31 | Speedel Pharma Ag | Procede de fabrication d'octanoylamides substitues |
| WO2003103653A1 (fr) * | 2002-06-11 | 2003-12-18 | Elan Pharmaceuticals, Inc. | Methodes de traitement de la maladie d'alzheimer par des amides d'acide aryl alcanoique |
| US20080234945A1 (en) * | 2005-07-25 | 2008-09-25 | Metanomics Gmbh | Means and Methods for Analyzing a Sample by Means of Chromatography-Mass Spectrometry |
| WO2009064479A1 (fr) | 2007-11-13 | 2009-05-22 | Teva Pharmaceutical Industries Ltd. | Formes polymorphes de l'hémifumarate d'aliskiren et procédé pour la préparation de celles-ci |
-
2011
- 2011-09-09 WO PCT/US2011/051076 patent/WO2012034065A1/fr active Application Filing
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5559111A (en) | 1994-04-18 | 1996-09-24 | Ciba-Geigy Corporation | δ-amino-γ-hydroxy-ω-aryl-alkanoic acid amides |
| US5606078A (en) | 1994-04-18 | 1997-02-25 | Ciba-Geigy Corporation | 3,5-Disubstituted tetrahydrofuran-2-ones |
| US6333198B1 (en) | 1998-06-10 | 2001-12-25 | Glaxo Wellcome, Inc. | Compound and its use |
| WO2002008172A1 (fr) * | 2000-07-25 | 2002-01-31 | Speedel Pharma Ag | Procede de fabrication d'octanoylamides substitues |
| WO2003103653A1 (fr) * | 2002-06-11 | 2003-12-18 | Elan Pharmaceuticals, Inc. | Methodes de traitement de la maladie d'alzheimer par des amides d'acide aryl alcanoique |
| US20080234945A1 (en) * | 2005-07-25 | 2008-09-25 | Metanomics Gmbh | Means and Methods for Analyzing a Sample by Means of Chromatography-Mass Spectrometry |
| WO2009064479A1 (fr) | 2007-11-13 | 2009-05-22 | Teva Pharmaceutical Industries Ltd. | Formes polymorphes de l'hémifumarate d'aliskiren et procédé pour la préparation de celles-ci |
Non-Patent Citations (4)
| Title |
|---|
| DRUGS OF THE FUTURE, vol. 26, no. 12, 2001, pages 1139 - 1148 |
| LINDSAY, K. B. ET AL., J. ORG. CHEM., vol. 71, 2006, pages 4766 - 4777 |
| SNYDER, L.R. ET AL.: "Introduction to Modern Liquid Chromatography", vol. 549, 1979, JOHN WILEY & SONS |
| STROBEL, H.A. ET AL.: "Chemical Instrumentation: A Systematic Approach", vol. 953, 1989, WILEY & SONS |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105294612A (zh) * | 2014-06-05 | 2016-02-03 | 山东威智医药工业有限公司 | 阿利克仑中间体及其制备方法和应用 |
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