OA12167A - Asymmetric synthesis of pregabalin. - Google Patents

Asymmetric synthesis of pregabalin. Download PDF

Info

Publication number: OA12167A
Authority: OA; OAPI
Prior art keywords: cyano; formula; sait; acid; cation
Prior art date: 2000-01-27

Application number

OA1200200227A

Other languages

English (en)

Inventor

Mark Joseph Burk

Om Prakash Goel

Marvin Simon Hoekstra

Thomas Frederick Mich

Thomas Arthur Mulhern

James Andres Ramsden

Original Assignee

Warner Lambert Co

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.)

2000-01-27

Filing date

2001-01-11

Publication date

2006-05-08

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26874236&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=OA12167(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2001-01-11 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2006-05-08 Publication of OA12167A publication Critical patent/OA12167A/en

Links

AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 title claims abstract description 48
229960001233 pregabalin Drugs 0.000 title claims abstract description 36
238000011914 asymmetric synthesis Methods 0.000 title description 3
238000004519 manufacturing process Methods 0.000 claims abstract description 5
238000000034 method Methods 0.000 claims description 48
229910052739 hydrogen Inorganic materials 0.000 claims description 32
239000000203 mixture Substances 0.000 claims description 31
238000006243 chemical reaction Methods 0.000 claims description 25
239000002253 acid Substances 0.000 claims description 24
239000003054 catalyst Substances 0.000 claims description 22
-1 (S)-3-cyano-5-methylhexanoic acid carboxylate Chemical class 0.000 claims description 19
150000001875 compounds Chemical class 0.000 claims description 16
125000000217 alkyl group Chemical group 0.000 claims description 15
MGWZYUMZVZMKTN-ZETCQYMHSA-N (3s)-3-cyano-5-methylhexanoic acid Chemical compound CC(C)C[C@H](C#N)CC(O)=O MGWZYUMZVZMKTN-ZETCQYMHSA-N 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 12
150000001768 cations Chemical class 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
229910052700 potassium Inorganic materials 0.000 claims description 12
239000011591 potassium Substances 0.000 claims description 12
125000004093 cyano group Chemical group *C#N 0.000 claims description 10
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
239000003446 ligand Substances 0.000 claims description 8
150000007942 carboxylates Chemical class 0.000 claims description 6
150000001336 alkenes Chemical class 0.000 claims description 5
150000001412 amines Chemical class 0.000 claims description 5
239000003513 alkali Substances 0.000 claims description 4
230000003197 catalytic effect Effects 0.000 claims 2
230000005588 protonation Effects 0.000 claims 2
125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 2
125000003277 amino group Chemical group 0.000 claims 1
150000001733 carboxylic acid esters Chemical class 0.000 claims 1
150000003141 primary amines Chemical class 0.000 claims 1
230000015572 biosynthetic process Effects 0.000 abstract description 15
238000003786 synthesis reaction Methods 0.000 abstract description 15
239000000543 intermediate Substances 0.000 abstract description 3
208000028017 Psychotic disease Diseases 0.000 abstract description 2
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206010015037 epilepsy Diseases 0.000 abstract description 2
208000027753 pain disease Diseases 0.000 abstract description 2
150000003839 salts Chemical class 0.000 abstract description 2
238000009876 asymmetric hydrogenation reaction Methods 0.000 abstract 1
230000002265 prevention Effects 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 131
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239000001257 hydrogen Substances 0.000 description 31
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239000010948 rhodium Substances 0.000 description 27
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
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ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
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238000004817 gas chromatography Methods 0.000 description 9
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JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 4
239000007858 starting material Substances 0.000 description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
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108091022930 Glutamate decarboxylase Proteins 0.000 description 3
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125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
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239000012267 brine Substances 0.000 description 1
244000309464 bull Species 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
OEERIBPGRSLGEK-UHFFFAOYSA-N carbon dioxide;methanol Chemical compound OC.O=C=O OEERIBPGRSLGEK-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
230000006315 carbonylation Effects 0.000 description 1
238000005810 carbonylation reaction Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
238000012777 commercial manufacturing Methods 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
230000002920 convulsive effect Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
YPJHNVOLWRBDQA-UHFFFAOYSA-N cyano hex-2-enoate Chemical compound CCCC=CC(=O)OC#N YPJHNVOLWRBDQA-UHFFFAOYSA-N 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
SGDINNZGYDHHKM-UHFFFAOYSA-N dilithium;trimethylsilylazanide Chemical compound [Li+].[Li+].C[Si](C)(C)[NH-].C[Si](C)(C)[NH-] SGDINNZGYDHHKM-UHFFFAOYSA-N 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
QKZWXPLBVCKXNQ-ROJLCIKYSA-N dipamp Chemical compound COC1=CC=CC=C1[P@@](C=1C=CC=CC=1)CC[P@@](C=1C(=CC=CC=1)OC)C1=CC=CC=C1 QKZWXPLBVCKXNQ-ROJLCIKYSA-N 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
WBQBMWWPFBMMOD-SECBINFHSA-N ethyl (3r)-3-cyano-5-methylhexanoate Chemical compound CCOC(=O)C[C@H](C#N)CC(C)C WBQBMWWPFBMMOD-SECBINFHSA-N 0.000 description 1
238000000605 extraction Methods 0.000 description 1
230000001815 facial effect Effects 0.000 description 1
238000011049 filling Methods 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
229960002989 glutamic acid Drugs 0.000 description 1
JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
231100001261 hazardous Toxicity 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
XXHDAWYDNSXJQM-UHFFFAOYSA-M hex-3-enoate Chemical compound CCC=CCC([O-])=O XXHDAWYDNSXJQM-UHFFFAOYSA-M 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
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000003993 interaction Effects 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
LVHBHZANLOWSRM-UHFFFAOYSA-N itaconic acid Chemical class OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
MMSQMDXHUFANGO-UHFFFAOYSA-N methyl 3-cyano-5-methylhex-3-enoate Chemical compound COC(=O)CC(C#N)=CC(C)C MMSQMDXHUFANGO-UHFFFAOYSA-N 0.000 description 1
BQCGQKLXPMPVDP-UHFFFAOYSA-N methyl 3-cyano-5-methylhexanoate Chemical compound COC(=O)CC(C#N)CC(C)C BQCGQKLXPMPVDP-UHFFFAOYSA-N 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification 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
FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
238000010979 pH adjustment Methods 0.000 description 1
229910052763 palladium Inorganic materials 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
125000005561 phenanthryl group Chemical group 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
229940094035 potassium bromide Drugs 0.000 description 1
XYLSFBDMLBNBMI-UHFFFAOYSA-M potassium;3-cyano-5-methylhex-3-enoate Chemical compound [K+].CC(C)C=C(C#N)CC([O-])=O XYLSFBDMLBNBMI-UHFFFAOYSA-M 0.000 description 1
AYXYPKUFHZROOJ-SSDOTTSWSA-N pregabalin Chemical compound CC(C)C[C@@H](CN)CC(O)=O AYXYPKUFHZROOJ-SSDOTTSWSA-N 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
238000012545 processing Methods 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
238000010926 purge Methods 0.000 description 1
239000012066 reaction slurry Substances 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
238000010189 synthetic method Methods 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
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
SCNWCHWHTLUICV-UHFFFAOYSA-N tert-butylazanium;3-cyano-5-methylhex-3-enoate Chemical compound CC(C)(C)[NH3+].CC(C)C=C(C#N)CC([O-])=O SCNWCHWHTLUICV-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
XXHDAWYDNSXJQM-ONEGZZNKSA-N trans-hex-3-enoic acid Chemical compound CC\C=C\CC(O)=O XXHDAWYDNSXJQM-ONEGZZNKSA-N 0.000 description 1
238000012546 transfer Methods 0.000 description 1
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/23—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and carboxyl groups, other than cyano groups, bound to the same unsaturated acyclic carbon skeleton
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/19—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and carboxyl groups, other than cyano groups, bound to the same saturated acyclic carbon skeleton

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Psychiatry (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Catalysts (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

OA1200200227A 2000-01-27 2001-01-11 Asymmetric synthesis of pregabalin. OA12167A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US17835900P	2000-01-27	2000-01-27
US19042700P	2000-03-17	2000-03-17

Publications (1)

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OA12167A true OA12167A (en)	2006-05-08

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OA1200200227A OA12167A (en)	2000-01-27	2001-01-11	Asymmetric synthesis of pregabalin.

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US (1)	US6891059B2 (fr)
EP (1)	EP1250311B1 (fr)
JP (2)	JP4235384B2 (fr)
KR (1)	KR100549748B1 (fr)
CN (1)	CN1210253C (fr)
AP (1)	AP1438A (fr)
AR (1)	AR028499A1 (fr)
AT (1)	ATE261930T1 (fr)
AU (1)	AU777046B2 (fr)
BG (1)	BG65560B1 (fr)
BR (1)	BRPI0107863B8 (fr)
CA (1)	CA2396090C (fr)
CO (1)	CO5251411A1 (fr)
CR (1)	CR6703A (fr)
CU (1)	CU23221A3 (fr)
CY (1)	CY2004011I1 (fr)
CZ (1)	CZ302838B6 (fr)
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ES (1)	ES2219493T3 (fr)
GE (1)	GEP20043236B (fr)
HN (1)	HN2001000010A (fr)
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IS (1)	IS2038B (fr)
MA (1)	MA26869A1 (fr)
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MX (1)	MXPA02007307A (fr)
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NO (1)	NO327958B1 (fr)
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OA (1)	OA12167A (fr)
PA (1)	PA8510501A1 (fr)
PE (1)	PE20011063A1 (fr)
PL (1)	PL203985B1 (fr)
PT (1)	PT1250311E (fr)
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SK (1)	SK287303B6 (fr)
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TN (1)	TNSN01016A1 (fr)
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TW (1)	TWI288128B (fr)
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CA2681313C (fr) *	2007-03-22	2012-09-11	Teva Pharmaceutical Industries Ltd.	Synthese de l'acide (s)-(+)-3-(aminomethyl)-5-methylhexanoique
US8168828B2 (en)	2007-06-25	2012-05-01	Msn Laboratories, Limited	Process for the preparation of pregabalin
KR100846419B1 (ko) *	2007-08-10	2008-07-15	한국과학기술원	프레가발린의 신규한 제조 방법
KR20090101462A (ko) *	2007-10-03	2009-09-28	테바 파마슈티컬 인더스트리즈 리미티드	프레가발린-4-엘리미네이트, 프레가발린 5-엘리미네이트, 기준 마커 및 표준물로서의 이들의 용도, 및 이들을 낮은 수준으로 함유하는 프레가발린의 제조 방법
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JP5526538B2 (ja) *	2008-01-10	2014-06-18	住友化学株式会社	３−（２−シアノ−１−プロペニル）−２，２−ジメチルシクロプロパンカルボン酸化合物の製造方法およびその中間体
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KR100491282B1 (ko) *	1996-07-24	2005-05-24	워너-램버트 캄파니 엘엘씨	통증 치료용 이소부틸가바 및 그의 유도체
US6127418A (en) *	1997-08-20	2000-10-03	Warner-Lambert Company	GABA analogs to prevent and treat gastrointestinal damage
AU1572399A (en)	1997-12-17	1999-07-05	Chirotech Technology Limited	Asymmetric hydrogenation
EP1070043B1 (fr)	1998-04-09	2004-02-18	Chirotech Technology Limited	Hydrogenation asymetrique
SK287303B6 (sk) *	2000-01-27	2010-06-07	Warner-Lambert Company	Spôsob prípravy derivátu (S)-3-kyano-5-metyl-hexánovej kyseliny, spôsob a medziprodukt na prípravu pregabalínu

2001
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2002
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Also Published As

Publication number	Publication date
IS6430A (is)	2002-06-19
TNSN01016A1 (fr)	2005-11-10
HU228815B1 (en)	2013-05-28
SI1250311T1 (en)	2004-10-31
EA200200642A1 (ru)	2002-12-26
TR200400953T4 (tr)	2004-07-21
HRP20020627A2 (en)	2004-08-31
BRPI0107863B8 (pt)	2017-04-25
CA2396090C (fr)	2006-01-10
SV2002000295A (es)	2002-06-07
BR0107863B1 (pt)	2013-06-18
YU56202A (sh)	2006-01-16
EP1250311B1 (fr)	2004-03-17
EE200200403A (et)	2003-10-15
NO20023582L (no)	2002-09-02
IL150633A (en)	2009-08-03
ES2219493T3 (es)	2004-12-01
CZ302838B6 (cs)	2011-12-07
PL357077A1 (en)	2004-07-12
CO5251411A1 (es)	2003-02-28
JP2009073841A (ja)	2009-04-09
KR20020073187A (ko)	2002-09-19
CU23221A3 (es)	2007-07-20
CZ20022520A3 (cs)	2002-10-16
DK1250311T3 (da)	2004-08-16
PL203985B1 (pl)	2009-11-30
KR100549748B1 (ko)	2006-02-08
SK10782002A3 (sk)	2002-11-06
HRP20020627B1 (hr)	2011-01-31
WO2001055090A1 (fr)	2001-08-02
HUP0204307A3 (en)	2003-07-28
AU777046B2 (en)	2004-09-30
AU2213801A (en)	2001-08-07
JP4235384B2 (ja)	2009-03-11
JP2003520841A (ja)	2003-07-08
AP2002002588A0 (en)	2002-09-30
EE05216B1 (et)	2009-10-15
BG106849A (en)	2003-03-31
JP4886753B2 (ja)	2012-02-29
UA75584C2 (uk)	2006-05-15
US6891059B2 (en)	2005-05-10
EP1250311A1 (fr)	2002-10-23
NO327958B1 (no)	2009-10-26
DE60102356D1 (de)	2004-04-22
MY127152A (en)	2006-11-30
HN2001000010A (es)	2001-06-13
BG65560B1 (bg)	2008-12-30
RS50257B (sr)	2009-07-15
PE20011063A1 (es)	2001-10-18
CN1396905A (zh)	2003-02-12
HUP0204307A2 (hu)	2003-06-28
ATE261930T1 (de)	2004-04-15
IL150633A0 (en)	2003-02-12
NO20023582D0 (no)	2002-07-26
MXPA02007307A (es)	2002-11-29
EA004934B1 (ru)	2004-10-28
US20030212290A1 (en)	2003-11-13
SK287303B6 (sk)	2010-06-07
DZ3268A1 (fr)	2001-08-02
IS2038B (is)	2005-08-15
MA26869A1 (fr)	2004-12-20
TWI288128B (en)	2007-10-11
CA2396090A1 (fr)	2001-08-02
CY2004011I1 (el)	2010-07-28
GEP20043236B (en)	2004-05-25
DE60102356T2 (de)	2005-02-17
CN1210253C (zh)	2005-07-13
PA8510501A1 (es)	2002-02-21
AP1438A (en)	2005-05-23
AR028499A1 (es)	2003-05-14
ME00921B (me)	2012-06-20
NZ519551A (en)	2004-02-27
BR0107863A (pt)	2002-11-05
PT1250311E (pt)	2004-07-30
EG24138A (en)	2008-08-06
CR6703A (es)	2003-06-24

Publication	Publication Date	Title
OA12167A (en)	2006-05-08	Asymmetric synthesis of pregabalin.
CZ296895B6 (cs)	2006-07-12	Zpusob prípravy kyseliny (+-)-3-(aminomethyl)-5-methylhexanové
JPH0987258A (ja)	1997-03-31	オキサゾリン類、その製造方法およびそれを用いる不斉シクロプロパンカルボン酸類の製造方法
KR100846419B1 (ko)	2008-07-15	프레가발린의 신규한 제조 방법
CN1329368C (zh)	2007-08-01	制备富含对映体的化合物的方法
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PL210934B1 (pl)	2012-03-30	Optycznie czynne pochodne bisoksazoliny, sposób wytwarzania tych związków, substraty i sposób ich wytwarzania
CN114456089B (zh)	2023-05-23	一种路易斯酸促进的烯烃和肟酯与胺的三组分反应方法
ZA200205878B (en)	2003-07-23	Asymmetric synthesis of pregabalin.
JP2025134168A (ja)	2025-09-17	銅触媒による立体特異的シアノ化反応
JPH0415776B2 (fr)	1992-03-19
HK1051679A1 (en)	2003-08-15	Asymmetric synthesis of pregabalin
HK1051679B (en)	2005-10-28	Asymmetric synthesis of pregabalin
JPH03506036A (ja)	1991-12-26	アルカンとホルメートとの反応によるカルボン酸の製造方法