CN1646525A - 5-[[2(r)-[1(r)-[3,5-双(三氟甲基)苯基]乙氧基]-3(s)-(4-氟苯基)-4-吗啉基]甲基]-1,2-二氢-3h-1,2,4-三唑-3-酮的制备方法 - Google Patents
5-[[2(r)-[1(r)-[3,5-双(三氟甲基)苯基]乙氧基]-3(s)-(4-氟苯基)-4-吗啉基]甲基]-1,2-二氢-3h-1,2,4-三唑-3-酮的制备方法 Download PDFInfo
- Publication number
- CN1646525A CN1646525A CNA038084465A CN03808446A CN1646525A CN 1646525 A CN1646525 A CN 1646525A CN A038084465 A CNA038084465 A CN A038084465A CN 03808446 A CN03808446 A CN 03808446A CN 1646525 A CN1646525 A CN 1646525A
- Authority
- CN
- China
- Prior art keywords
- formula
- compounds
- compound
- preparation
- mineral alkali
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 20
- ATALOFNDEOCMKK-OITMNORJSA-N aprepitant Chemical compound O([C@@H]([C@@H]1C=2C=CC(F)=CC=2)O[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CCN1CC1=NNC(=O)N1 ATALOFNDEOCMKK-OITMNORJSA-N 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 41
- 238000002360 preparation method Methods 0.000 claims abstract description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 239000003513 alkali Substances 0.000 claims description 9
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 9
- 235000010755 mineral Nutrition 0.000 claims description 9
- 239000011707 mineral Substances 0.000 claims description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 5
- 235000015320 potassium carbonate Nutrition 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 229940125782 compound 2 Drugs 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims 3
- 102100024304 Protachykinin-1 Human genes 0.000 abstract description 4
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 abstract description 3
- 101800003906 Substance P Proteins 0.000 abstract description 3
- 239000002464 receptor antagonist Substances 0.000 abstract description 3
- 229940044551 receptor antagonist Drugs 0.000 abstract description 3
- 206010047700 Vomiting Diseases 0.000 abstract description 2
- 208000027866 inflammatory disease Diseases 0.000 abstract description 2
- 208000020016 psychiatric disease Diseases 0.000 abstract description 2
- 101000831616 Homo sapiens Protachykinin-1 Proteins 0.000 abstract 1
- ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- -1 (trifluoromethyl) phenyl Chemical group 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000000203 mixture Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- DNUJVGBNIXGTHC-UHFFFAOYSA-N 3,6-dihydro-2h-oxazine Chemical compound C1NOCC=C1 DNUJVGBNIXGTHC-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 description 1
- 150000001411 amidrazones Chemical class 0.000 description 1
- 229960001372 aprepitant Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- 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]
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
- C07D265/32—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings with oxygen atoms directly attached to ring carbon atoms
Abstract
Description
Claims (14)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US37373402P | 2002-04-18 | 2002-04-18 | |
US60/373,734 | 2002-04-18 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1646525A true CN1646525A (zh) | 2005-07-27 |
CN1293077C CN1293077C (zh) | 2007-01-03 |
Family
ID=29251070
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB038084465A Expired - Fee Related CN1293077C (zh) | 2002-04-18 | 2003-04-17 | 5-[[2(r)-[1(r)-[3,5-双(三氟甲基)苯基]乙氧基]-3(s)-(4-氟苯基)-4-吗啉基]甲基]-1,2-二氢-3h-1,2,4-三唑-3-酮的制备方法 |
Country Status (21)
Country | Link |
---|---|
US (1) | US7847095B2 (zh) |
EP (1) | EP1499611B1 (zh) |
JP (1) | JP4271586B2 (zh) |
KR (1) | KR100982901B1 (zh) |
CN (1) | CN1293077C (zh) |
AR (1) | AR039625A1 (zh) |
AU (1) | AU2003228578B2 (zh) |
BR (1) | BR0309277A (zh) |
CA (1) | CA2482466C (zh) |
EG (1) | EG24127A (zh) |
HR (1) | HRP20040974A2 (zh) |
IL (1) | IL164586A (zh) |
MX (1) | MXPA04010182A (zh) |
NO (1) | NO330362B1 (zh) |
NZ (1) | NZ535883A (zh) |
PL (1) | PL217076B1 (zh) |
RU (1) | RU2326879C2 (zh) |
TW (1) | TWI341313B (zh) |
UA (1) | UA84399C2 (zh) |
WO (1) | WO2003089429A1 (zh) |
ZA (1) | ZA200408193B (zh) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102939285A (zh) * | 2010-05-24 | 2013-02-20 | 成都地奥制药集团有限公司 | 5-[[2(r)-[1(r)-[3,5-双(三氟甲基)苯基]乙氧基]-3(s)-4-(氟苯基)-4-吗啉基]甲基]-1,2-二氢-3h-1,2,4-三唑-3-酮的制备方法 |
CN103030668A (zh) * | 2011-10-09 | 2013-04-10 | 江苏豪森药业股份有限公司 | 一种制备福沙匹坦二甲葡胺的方法 |
CN103097379A (zh) * | 2010-06-18 | 2013-05-08 | 成药技术Ip控股(泽西)有限公司 | 纳米结构的阿瑞匹坦组合物、其制备方法以及包含其的药物组合物 |
CN103288813A (zh) * | 2013-06-04 | 2013-09-11 | 四川百利药业有限责任公司 | 一种阿瑞匹坦的制备方法 |
CN106967057A (zh) * | 2017-06-01 | 2017-07-21 | 四川制药制剂有限公司 | 一种阿瑞匹坦高效制备工艺 |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE0400850D0 (sv) * | 2004-03-30 | 2004-03-31 | Astrazeneca Ab | Novel Compounds |
US8080656B2 (en) | 2005-10-05 | 2011-12-20 | Ranbaxy Laboratories Limited | Process for the preparation of aprepitant |
US8133994B2 (en) * | 2005-10-06 | 2012-03-13 | Dr. Reddy's Laboratories Ltd. | Preparation of aprepitant |
US9227958B2 (en) | 2006-02-03 | 2016-01-05 | Glenmark Pharmaceuticals Limited | Amorphous and crystalline forms of aprepitant and processes for the preparation thereof |
WO2008026216A2 (en) * | 2006-08-28 | 2008-03-06 | Hetero Drugs Limited | Process for purification of aprepitant |
WO2012146692A1 (en) | 2011-04-29 | 2012-11-01 | Sandoz Ag | Novel intermediates for the preparation of highly pure aprepitant or fosaprepitant |
WO2013124823A1 (en) * | 2012-02-23 | 2013-08-29 | Piramal Enterprises Limited | An improved process for the preparation of aprepitant |
CZ304770B6 (cs) * | 2012-03-13 | 2014-10-08 | Zentiva, K.S. | Způsob výroby 3-(((2R,3S)-2-((R)-1-(3,5-bis(trifluormethyl)fenyl)ethoxy)-3-(4-fluorfenyl)morfolino)methyl)-1H-1,2,4-triazol-5(4H)-onu (Aprepitantu) v polymorfní formě II |
ITMI20130273A1 (it) * | 2013-02-26 | 2014-08-27 | Olon Spa | Procedimento per la preparazione di aprepitant |
CN107954998B (zh) * | 2016-10-14 | 2022-08-12 | 江苏豪森药业集团有限公司 | 福沙匹坦中间体的制备方法 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5719147A (en) | 1992-06-29 | 1998-02-17 | Merck & Co., Inc. | Morpholine and thiomorpholine tachykinin receptor antagonists |
US5637699A (en) | 1992-06-29 | 1997-06-10 | Merck & Co., Inc. | Process for preparing morpholine tachykinin receptor antagonists |
IL111960A (en) * | 1993-12-17 | 1999-12-22 | Merck & Co Inc | Morpholines and thiomorpholines their preparation and pharmaceutical compositions containing them |
TW385308B (en) * | 1994-03-04 | 2000-03-21 | Merck & Co Inc | Prodrugs of morpholine tachykinin receptor antagonists |
GB9513972D0 (en) * | 1995-07-08 | 1995-09-06 | Merck Sharp & Dohme | Pharmaceutical compositions |
ZA985765B (en) | 1997-07-02 | 1999-08-04 | Merck & Co Inc | Polymorphic form of a tachykinin receptor antagonist. |
GB9813025D0 (en) | 1998-06-16 | 1998-08-12 | Merck Sharp & Dohme | Chemical synthesis |
-
2003
- 2003-04-09 AR ARP030101248A patent/AR039625A1/es not_active Application Discontinuation
- 2003-04-10 TW TW092108229A patent/TWI341313B/zh not_active IP Right Cessation
- 2003-04-17 UA UA20041109407A patent/UA84399C2/ru unknown
- 2003-04-17 RU RU2004133678/04A patent/RU2326879C2/ru not_active IP Right Cessation
- 2003-04-17 AU AU2003228578A patent/AU2003228578B2/en not_active Ceased
- 2003-04-17 PL PL373348A patent/PL217076B1/pl unknown
- 2003-04-17 JP JP2003586150A patent/JP4271586B2/ja not_active Expired - Fee Related
- 2003-04-17 US US10/511,691 patent/US7847095B2/en active Active
- 2003-04-17 CN CNB038084465A patent/CN1293077C/zh not_active Expired - Fee Related
- 2003-04-17 NZ NZ535883A patent/NZ535883A/en not_active IP Right Cessation
- 2003-04-17 MX MXPA04010182A patent/MXPA04010182A/es active IP Right Grant
- 2003-04-17 EP EP03726338.1A patent/EP1499611B1/en not_active Expired - Lifetime
- 2003-04-17 KR KR1020047016622A patent/KR100982901B1/ko not_active IP Right Cessation
- 2003-04-17 CA CA2482466A patent/CA2482466C/en not_active Expired - Fee Related
- 2003-04-17 BR BR0309277-1A patent/BR0309277A/pt not_active IP Right Cessation
- 2003-04-17 WO PCT/US2003/011956 patent/WO2003089429A1/en active Application Filing
- 2003-04-19 EG EG2003040353A patent/EG24127A/xx active
-
2004
- 2004-10-11 ZA ZA200408193A patent/ZA200408193B/en unknown
- 2004-10-14 IL IL164586A patent/IL164586A/en not_active IP Right Cessation
- 2004-10-15 HR HR20040974A patent/HRP20040974A2/hr not_active Application Discontinuation
- 2004-11-17 NO NO20045001A patent/NO330362B1/no not_active IP Right Cessation
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102939285A (zh) * | 2010-05-24 | 2013-02-20 | 成都地奥制药集团有限公司 | 5-[[2(r)-[1(r)-[3,5-双(三氟甲基)苯基]乙氧基]-3(s)-4-(氟苯基)-4-吗啉基]甲基]-1,2-二氢-3h-1,2,4-三唑-3-酮的制备方法 |
CN102939285B (zh) * | 2010-05-24 | 2014-12-24 | 成都地奥制药集团有限公司 | 5-[[2(r)-[1(r)-[3,5-双(三氟甲基)苯基]乙氧基]-3(s)-4-(氟苯基)-4-吗啉基]甲基]-1,2-二氢-3h-1,2,4-三唑-3-酮的制备方法 |
US8940890B2 (en) | 2010-05-24 | 2015-01-27 | Chengdu Di'ao Pharmaceutical Group Co., Ltd. | Preparation method of 5-[[2(R)-[1(R)-[3,5-bis(trifluoromethyl) phenyl]ethoxy]-3(S)-4-fluorophenyl-4-morpholinyl]methyl]-1,2-dihydro-3H-1,2,4-triazole-3-one |
CN103097379A (zh) * | 2010-06-18 | 2013-05-08 | 成药技术Ip控股(泽西)有限公司 | 纳米结构的阿瑞匹坦组合物、其制备方法以及包含其的药物组合物 |
CN103030668A (zh) * | 2011-10-09 | 2013-04-10 | 江苏豪森药业股份有限公司 | 一种制备福沙匹坦二甲葡胺的方法 |
CN103030668B (zh) * | 2011-10-09 | 2016-06-15 | 江苏豪森药业集团有限公司 | 一种制备福沙匹坦二甲葡胺的方法 |
CN103288813A (zh) * | 2013-06-04 | 2013-09-11 | 四川百利药业有限责任公司 | 一种阿瑞匹坦的制备方法 |
CN106967057A (zh) * | 2017-06-01 | 2017-07-21 | 四川制药制剂有限公司 | 一种阿瑞匹坦高效制备工艺 |
Also Published As
Publication number | Publication date |
---|---|
EP1499611B1 (en) | 2015-02-11 |
CN1293077C (zh) | 2007-01-03 |
PL373348A1 (en) | 2005-08-22 |
RU2004133678A (ru) | 2005-05-27 |
JP2005529881A (ja) | 2005-10-06 |
AR039625A1 (es) | 2005-03-02 |
IL164586A0 (en) | 2005-12-18 |
KR20050007299A (ko) | 2005-01-17 |
EP1499611A1 (en) | 2005-01-26 |
JP4271586B2 (ja) | 2009-06-03 |
ZA200408193B (en) | 2006-06-28 |
CA2482466A1 (en) | 2003-10-30 |
IL164586A (en) | 2010-11-30 |
RU2326879C2 (ru) | 2008-06-20 |
TWI341313B (en) | 2011-05-01 |
KR100982901B1 (ko) | 2010-09-20 |
HRP20040974A2 (en) | 2005-06-30 |
AU2003228578B2 (en) | 2009-07-30 |
AU2003228578A1 (en) | 2003-11-03 |
PL217076B1 (pl) | 2014-06-30 |
US20050215786A1 (en) | 2005-09-29 |
BR0309277A (pt) | 2005-02-22 |
US7847095B2 (en) | 2010-12-07 |
EG24127A (en) | 2008-07-08 |
NO20045001L (no) | 2004-11-17 |
EP1499611A4 (en) | 2006-05-03 |
WO2003089429A1 (en) | 2003-10-30 |
CA2482466C (en) | 2012-11-20 |
MXPA04010182A (es) | 2005-02-03 |
TW200400189A (en) | 2004-01-01 |
UA84399C2 (en) | 2008-10-27 |
NZ535883A (en) | 2007-12-21 |
NO330362B1 (no) | 2011-04-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1293077C (zh) | 5-[[2(r)-[1(r)-[3,5-双(三氟甲基)苯基]乙氧基]-3(s)-(4-氟苯基)-4-吗啉基]甲基]-1,2-二氢-3h-1,2,4-三唑-3-酮的制备方法 | |
EP2771005B1 (en) | Inhibitors of the renal outer medullary potassium channel | |
EP2771004B1 (en) | Inhibitors of the renal outer medullary potassium channel | |
CN1906191A (zh) | 制备方法 | |
JP2009544599A (ja) | Bace阻害剤として有用な大環状化合物 | |
EP2697209B1 (en) | Method for the preparation of substituted oxazolidinones | |
JP6169623B2 (ja) | アプレピタントの調製のための改良された製造方法 | |
AU6140199A (en) | Process for the synthesis of n-benzyl-3-(4-fluorophenyl)-1,4-oxazin-2-one | |
KR100576336B1 (ko) | 세팔로스포린 유도체의 제조방법 | |
JP2000026408A (ja) | 対掌体的に純粋なピロリジン誘導体、その塩、それらの製造方法 | |
KR102134179B1 (ko) | 카보네이트를 이용한 시탈로프람 및 에스시탈로프람의 새로운 제조 방법 | |
CN1079793C (zh) | 对映体纯取代1,4-二氢吡啶-3,5-二羧酸衍生物的制备方法 | |
JP2675924B2 (ja) | アミノケトン類の製造方法 | |
CN1153777A (zh) | 1-芳基-4-氨基甲酰基四唑啉酮的制备方法 | |
JP2010100566A (ja) | 三環性ヘテロアリール化合物を含有する医薬 | |
JP2008273840A (ja) | ベンジルアミン誘導体の製造法 | |
CN1481362A (zh) | 制备二芳基-4-氨基-哌啶基化合物的新方法 | |
WO2002030893A1 (fr) | Procedes permettant de produire un compose pour la production de composes antibacteriens et produit intermediaire utilise | |
KR20050041250A (ko) | 3-(z)-프로페닐 세펨 유도체의 제조방법 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C56 | Change in the name or address of the patentee |
Owner name: MERCK + CO INC Free format text: FORMER NAME: MIKE COMPANY |
|
CP01 | Change in the name or title of a patent holder |
Address after: New jersey, USA Co-patentee after: MERCK SHARP & DOHME Ltd. Patentee after: MERCK SHARP & DOHME Corp. Address before: New jersey, USA Co-patentee before: Merck Sharp & Dohme Ltd. Patentee before: MERCK & Co.,Inc. |
|
ASS | Succession or assignment of patent right |
Owner name: SCHERING CORP (US) Free format text: FORMER OWNER: MSD CORP. Effective date: 20121026 |
|
C41 | Transfer of patent application or patent right or utility model | ||
C56 | Change in the name or address of the patentee |
Owner name: MSD CORP. Free format text: FORMER NAME: SCHERING CORP (US) |
|
CP01 | Change in the name or title of a patent holder |
Address after: New jersey, USA Patentee after: MERCK SHARP & DOHME Corp. Patentee after: MERCK SHARP & DOHME Ltd. Address before: New jersey, USA Patentee before: SCHERING Corp. Patentee before: Merck Sharp & Dohme Ltd. |
|
TR01 | Transfer of patent right |
Effective date of registration: 20121026 Address after: New jersey, USA Patentee after: SCHERING Corp. Patentee after: MERCK SHARP & DOHME Ltd. Address before: New jersey, USA Patentee before: MERCK SHARP & DOHME Corp. Patentee before: Merck Sharp & Dohme Ltd. |
|
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070103 Termination date: 20150417 |
|
EXPY | Termination of patent right or utility model |