DK2229359T3 - Fremgangsmåde til fremstilling af et indolinonderivat - Google Patents
Fremgangsmåde til fremstilling af et indolinonderivat Download PDFInfo
- Publication number
- DK2229359T3 DK2229359T3 DK08857477.7T DK08857477T DK2229359T3 DK 2229359 T3 DK2229359 T3 DK 2229359T3 DK 08857477 T DK08857477 T DK 08857477T DK 2229359 T3 DK2229359 T3 DK 2229359T3
- Authority
- DK
- Denmark
- Prior art keywords
- compound
- formula
- methyl
- reaction
- mol
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Claims (8)
1. Fremgangsmåde til fremstilling af en forbindelse med formlen
omfattende trinnet at omsætte en forbindelse med formlen
med en forbindelse med formlen
i protiske eller aromatiske opløsningsmidler eller i blandinger af disse opløsningsmidler med stærkt polære opløsningsmidler ved en temperatur på ikke under 50°C under tilbagesvalingsbetingelser, kendetegnet ved, at forbindelsen med formlen
opnås ved basekatalyseret dechloracetylering af en forbindelse med formlen
i protiske opløsningsmidler ved temperaturer på cirka 70°C til omgivelsernes temperatur under anvendelse af uorganiske eller organiske baser som katalysator.
2. Fremgangsmåde ifølge krav 1, i hvilken forbindelsen med formlen
opnås ved at omsætte en forbindelse med formlen
med en forbindelse med formlen
og efterfølgende hydrogenering af nitrogruppen til en aminogruppe.
3. Fremgangsmåde ifølge krav 2, i hvilken forbindelsen med formlen
opnås ved at omsætte en forbindelse med formlen
med en forbindelse med formlen
4. Fremgangsmåde ifølge et hviket som helst af kravene 1 til 3, i hvilken forbindelsen med formlen
opnås ved at omsætte en forbindelse med formlen
med en forbindelse med formlen
5. Fremgangsmåde ifølge krav 4, i hvilken forbindelsen med formlen
opnås ved at omsætte en forbindelse med formlen
med en forbindelse med formlen
6. Fremgangsmåde ifølge krav 5, i hvilken forbindelsen med formlen
opnås ved følgende trin: (i) at forestre en forbindelse med formlen
til opnåelse af en forbindelse med formlen
(ii) at omsætte produktet af reaktionen (i) med malonsyredimethylester til opnåelse af en forbindelse med formlen
(iii) at foretage cyklisering af produktet af reaktionen (ii) ved en hydrogeneringsreaktion.
7. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 6, i hvilken forbindelsen med formlen
omsættes med EtSOsH for at opnå et monoethansulfonatsalt af denne forbindelse.
8. Fremgangsmåde ifølge krav 7, som yderligere omfatter et trin med formaling af monoethansulfonatsaltet af forbindelsen.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP07122122 | 2007-12-03 | ||
PCT/EP2008/066580 WO2009071523A1 (en) | 2007-12-03 | 2008-12-02 | Process for the manufacture of an indolinone derivative |
Publications (1)
Publication Number | Publication Date |
---|---|
DK2229359T3 true DK2229359T3 (da) | 2018-02-05 |
Family
ID=40452557
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK08857477.7T DK2229359T3 (da) | 2007-12-03 | 2008-12-02 | Fremgangsmåde til fremstilling af et indolinonderivat |
Country Status (21)
Country | Link |
---|---|
US (1) | US8304541B2 (da) |
EP (1) | EP2229359B1 (da) |
JP (1) | JP5269907B2 (da) |
KR (1) | KR20100094497A (da) |
CN (1) | CN101883756A (da) |
AR (1) | AR069530A1 (da) |
AU (1) | AU2008333286B2 (da) |
BR (1) | BRPI0820689A2 (da) |
CA (1) | CA2706423A1 (da) |
CL (1) | CL2008003598A1 (da) |
DK (1) | DK2229359T3 (da) |
ES (1) | ES2658091T3 (da) |
HU (1) | HUE036390T2 (da) |
IL (1) | IL205389A (da) |
MX (1) | MX2010005556A (da) |
NZ (1) | NZ585799A (da) |
PL (1) | PL2229359T3 (da) |
RU (1) | RU2525114C2 (da) |
TR (1) | TR201802086T4 (da) |
TW (1) | TWI432424B (da) |
WO (1) | WO2009071523A1 (da) |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
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PE20091445A1 (es) * | 2007-12-03 | 2009-10-19 | Boehringer Ingelheim Int | Derivados de indolinona y procedimiento para su fabricacion |
US20170065529A1 (en) | 2015-09-09 | 2017-03-09 | Boehringer Ingelheim International Gmbh | Pharmaceutical dosage form for immediate release of an indolinone derivative |
WO2012068441A2 (en) | 2010-11-19 | 2012-05-24 | Ratiopharm Gmbh | Intedanib salts and solid state forms thereof |
US20140350022A1 (en) | 2013-05-10 | 2014-11-27 | Boehringer Ingelheim International Gmbh | Efficacious treatment of NSCLC and predictive clinical marker of the responsiveness of a tumour to a treatment |
CN104829596B (zh) * | 2014-02-10 | 2017-02-01 | 石家庄以岭药业股份有限公司 | 吡咯取代吲哚酮类衍生物、其制备方法、包含该衍生物的组合物、及其用途 |
CN104262232B (zh) * | 2014-09-09 | 2016-05-04 | 苏州明锐医药科技有限公司 | 尼泰达尼的制备方法 |
CN106008308A (zh) * | 2015-03-13 | 2016-10-12 | 正大天晴药业集团股份有限公司 | 尼达尼布乙磺酸盐结晶 |
WO2016178064A1 (en) * | 2015-05-06 | 2016-11-10 | Suven Life Sciences Limited | Polymorph of nintedanib ethanesulphonate, processes and intermediates thereof |
CN104844499B (zh) * | 2015-06-05 | 2017-03-08 | 北京康立生医药技术开发有限公司 | 一锅法制备尼达尼布的合成方法 |
CN105126909B (zh) * | 2015-07-13 | 2018-01-23 | 淮海工学院 | 固载钯催化剂在4‑苯乙炔基‑3‑硝基苯甲酸甲酯合成中的应用 |
CN105001143A (zh) * | 2015-07-24 | 2015-10-28 | 南京正大天晴制药有限公司 | 一种制备高纯度乙磺酸尼达尼布的方法 |
CZ308695B6 (cs) | 2015-07-29 | 2021-03-03 | Zentiva, K.S. | Způsob přípravy methyl (Z)-3[[4-[methyl[2-(4-methyl-1piperazinyl)acetyl]amino]fenyl]amino]fenylmethylen)-oxindol-6karboxylátu (intedanibu, nintedanibu) |
CN106432042A (zh) * | 2015-08-13 | 2017-02-22 | 南京华威医药科技开发有限公司 | 尼达尼布乙磺酸水合物的药物新晶型 |
CN106467500A (zh) * | 2015-08-14 | 2017-03-01 | 廊坊百瑞化工有限公司 | 一种一锅煮法合成尼达尼布关键中间体的新方法 |
WO2017077551A2 (en) * | 2015-11-03 | 2017-05-11 | Mylan Laboratories Limited | An amorphous nintedanib esylate and solid dispersion thereof |
CN105418483A (zh) * | 2015-12-15 | 2016-03-23 | 南京艾德凯腾生物医药有限责任公司 | 一种结晶型乙磺酸尼达尼布的制备方法 |
CN105461609B (zh) * | 2015-12-25 | 2019-08-23 | 杭州新博思生物医药有限公司 | 一种尼达尼布的制备方法 |
CN105837493B (zh) * | 2016-04-08 | 2018-12-14 | 东南大学 | 尼达尼布的合成方法及其中间体 |
WO2017198202A1 (zh) * | 2016-05-19 | 2017-11-23 | 上海诚妙医药科技有限公司 | 尼达尼布的新晶型及其制备方法及其用途 |
CN106543069A (zh) * | 2016-09-20 | 2017-03-29 | 北京万全德众医药生物技术有限公司 | 6‑甲氧基羰基‑2‑氧代二氢吲哚的制备 |
CN107935909B (zh) * | 2016-10-13 | 2023-03-17 | 上海科胜药物研发有限公司 | 一种尼达尼布(nintedanib)及其中间体的合成方法 |
US10836751B2 (en) | 2016-10-12 | 2020-11-17 | Zhejiang Huahai Pharmaceutical Co., Ltd. | Methods for preparing Nintedanib and intermediates thereof |
CN108610308A (zh) * | 2016-12-09 | 2018-10-02 | 上海奥博生物医药技术有限公司 | 一锅法制备尼达尼布中间体的方法 |
CN110072849A (zh) * | 2017-03-14 | 2019-07-30 | 新源生物科技股份有限公司 | 3-z-[1-(4-(n-((4-甲基-哌嗪-1-基)-甲羰基)-n-甲基-氨基)-苯氨基)-1-苯基-亚甲基]-6-甲氧羰基-2-吲哚满酮的晶型 |
CN106841495B (zh) * | 2017-04-21 | 2018-05-11 | 常州佳德医药科技有限公司 | 乙磺酸尼达尼布中基因毒性杂质的高灵敏度分析方法 |
WO2019097112A1 (en) | 2017-11-17 | 2019-05-23 | Fermion Oy | Synthesis of a 2-indolinone derivative known as intermediate for preparing nintedanib |
CN110746378B (zh) * | 2018-12-03 | 2021-11-05 | 江苏豪森药业集团有限公司 | 一种胺基中间体的制备方法 |
CN111004141B (zh) * | 2019-12-19 | 2022-10-04 | 苏州诚和医药化学有限公司 | 一种尼达尼布中间体2-氯-n-甲基-n-(4-硝基苯基)乙酰胺合成新方法 |
CN115181078A (zh) * | 2022-07-27 | 2022-10-14 | 安徽修一制药有限公司 | 一种尼达尼布关键中间体的合成方法 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL141622A0 (en) * | 1998-09-25 | 2002-03-10 | Boehringer Ingelheim Pharma | Novel substituted indolinones with an inhibitory effect on various kinases and cyclin/cdk complexes |
UA75054C2 (uk) * | 1999-10-13 | 2006-03-15 | Бьорінгер Інгельхайм Фарма Гмбх & Ко. Кг | Заміщені в положенні 6 індолінони, їх одержання та їх застосування як лікарського засобу |
DE10233500A1 (de) * | 2002-07-24 | 2004-02-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 3-Z-[1-(4-(N-((4-Methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylen]-6-methoxycarbonyl-2-indolinon-Monoethansulfonat und dessen Verwendung als Arzneimittel |
US7148249B2 (en) | 2002-09-12 | 2006-12-12 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Indolinones substituted by heterocycles, the preparation thereof and their use as medicaments |
-
2008
- 2008-12-02 CA CA2706423A patent/CA2706423A1/en not_active Abandoned
- 2008-12-02 AR ARP080105253A patent/AR069530A1/es unknown
- 2008-12-02 DK DK08857477.7T patent/DK2229359T3/da active
- 2008-12-02 NZ NZ585799A patent/NZ585799A/en not_active IP Right Cessation
- 2008-12-02 RU RU2010126906/04A patent/RU2525114C2/ru not_active IP Right Cessation
- 2008-12-02 AU AU2008333286A patent/AU2008333286B2/en not_active Ceased
- 2008-12-02 CL CL2008003598A patent/CL2008003598A1/es unknown
- 2008-12-02 MX MX2010005556A patent/MX2010005556A/es active IP Right Grant
- 2008-12-02 TR TR2018/02086T patent/TR201802086T4/tr unknown
- 2008-12-02 WO PCT/EP2008/066580 patent/WO2009071523A1/en active Application Filing
- 2008-12-02 ES ES08857477.7T patent/ES2658091T3/es active Active
- 2008-12-02 BR BRPI0820689A patent/BRPI0820689A2/pt not_active IP Right Cessation
- 2008-12-02 CN CN2008801190699A patent/CN101883756A/zh active Pending
- 2008-12-02 EP EP08857477.7A patent/EP2229359B1/en active Active
- 2008-12-02 KR KR1020107012140A patent/KR20100094497A/ko not_active Application Discontinuation
- 2008-12-02 PL PL08857477T patent/PL2229359T3/pl unknown
- 2008-12-02 JP JP2010535406A patent/JP5269907B2/ja active Active
- 2008-12-02 TW TW097146810A patent/TWI432424B/zh not_active IP Right Cessation
- 2008-12-02 US US12/745,796 patent/US8304541B2/en active Active
- 2008-12-02 HU HUE08857477A patent/HUE036390T2/hu unknown
-
2010
- 2010-04-28 IL IL205389A patent/IL205389A/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
AR069530A1 (es) | 2010-01-27 |
AU2008333286A1 (en) | 2009-06-11 |
RU2525114C2 (ru) | 2014-08-10 |
TWI432424B (zh) | 2014-04-01 |
CL2008003598A1 (es) | 2010-02-12 |
IL205389A0 (en) | 2010-12-30 |
KR20100094497A (ko) | 2010-08-26 |
EP2229359B1 (en) | 2017-11-29 |
CA2706423A1 (en) | 2009-06-11 |
WO2009071523A1 (en) | 2009-06-11 |
BRPI0820689A2 (pt) | 2019-09-24 |
JP2011504919A (ja) | 2011-02-17 |
NZ585799A (en) | 2012-04-27 |
US20110201812A1 (en) | 2011-08-18 |
TW200932739A (en) | 2009-08-01 |
MX2010005556A (es) | 2010-08-11 |
US8304541B2 (en) | 2012-11-06 |
EP2229359A1 (en) | 2010-09-22 |
CN101883756A (zh) | 2010-11-10 |
ES2658091T3 (es) | 2018-03-08 |
HUE036390T2 (hu) | 2018-07-30 |
JP5269907B2 (ja) | 2013-08-21 |
TR201802086T4 (tr) | 2018-03-21 |
PL2229359T3 (pl) | 2018-04-30 |
IL205389A (en) | 2014-11-30 |
RU2010126906A (ru) | 2012-01-10 |
AU2008333286B2 (en) | 2014-08-14 |
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