HRP20200426T1 - Postupak za pripremu 1-(4-(4-(3,4-dikloro-2-fluorofenilamino)-7-metoksikinazolin-6-iloksi)piperi din-1-il)-prop-2-en-1-on hidroklorida i posrednici koji se koriste - Google Patents
Postupak za pripremu 1-(4-(4-(3,4-dikloro-2-fluorofenilamino)-7-metoksikinazolin-6-iloksi)piperi din-1-il)-prop-2-en-1-on hidroklorida i posrednici koji se koriste Download PDFInfo
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- HRP20200426T1 HRP20200426T1 HRP20200426TT HRP20200426T HRP20200426T1 HR P20200426 T1 HRP20200426 T1 HR P20200426T1 HR P20200426T T HRP20200426T T HR P20200426TT HR P20200426 T HRP20200426 T HR P20200426T HR P20200426 T1 HRP20200426 T1 HR P20200426T1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Claims (18)
1. Postupak za pripremu 1-(4-(4-(3,4-dikloro-2-fluorofenilamino)-7-metoksikinazolin-6-iloksi)piperdin-1-il)-prop-2-en-1-on hidroklorida formule (I), koji obuhvaća korake:
(1) podvrgavanje spoja formule (VIII) reakciji s halogenirajućim sredstvom u prisutnosti organske baze, nakon čega slijedi reakcija sa spojem formule (X), čime se dobiva spoj formule (VI);
(2) podvrgavanje spoja formule (VI) reakciji s otopinom amonijaka u polarnom protonskom otapalu, čime se dobiva spoj formule (V);
(3) podvrgavanje spoja formule (V) reakciji sa spojem formule (IX) u inertnom polarnom aprotičkom otapalu u prisutnosti baze, čime se dobije spoj formule (IV);
(4) podvrgavanje spoja formule (IV) reakciji s klorovodičnom kiselinom u inertnom otapalu, čime se dobiva spoj formule (III);
(5) podvrgavanje spoja formule (III) reakciji akrilacije sa
[image]
(pri čemu je X halogen) u prisutnosti baze, da se dobije spoj formule (II); i
(6) podvrgavanje spoja formule (II) reakciji s klorovodičnom kiselinom radi dobivanja spoja formule (I):
[image]
[image]
[image]
[image]
[image]
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[image]
2. Postupak prema zahtjevu 1, naznačen time što se korak (1) provodi u otapalu koje je odabrano iz skupine koja se sastoji od toluena, benzena i njihove smjese.
3. Postupak prema zahtjevu 1, naznačen time da je navedena organska baza u koraku (1) odabrana iz skupine koja se sastoji od diizopropilamina, trietilamina, diizopropil etilamina, dietilamina, piridina, 4-dimetilpiridina, morfolina i njihove smjese.
4. Postupak prema zahtjevu 1, naznačen time što je navedeno halogenirajuće sredstvo u koraku (1) izabrano iz skupine koja se sastoji od tionil klorida, fosforuzoksi klorida i njihove smjese.
5. Postupak prema zahtjevu 1, naznačen time da je navedeno polarno protonsko otapalo u koraku (2) izabrano iz skupine koja se sastoji od metanola, etanola, propanola i njihove smjese.
6. Postupak prema zahtjevu 1, naznačen time da je rečeno inertno polarno aprotično otapalo u koraku (3) izabrano iz skupine koja se sastoji od N, N-dimetilformamida, N, N-dimetilacetamida, N-metilpirolidin-2-ona, dimetil sulfoksida i a njihova smjesa.
7. Postupak prema zahtjevu 1, naznačen time da je baza u koraku (3) karbonatna sol alkalijskog metala odabrana iz skupine koju čine natrijev hidrogenkarbonat, kalijev karbonat, cezij karbonat i njihova smjesa.
8. Metoda iz zahtjeva 7, naznačena time, da se navedena baza koristi u količini od 1 do 5 molnih ekvivalenata na osnovi 1 mol ekvivalenta spoja formule (V).
9. Postupak prema zahtjevu 1, naznačen time da je rečeno inertno otapalo u koraku (4) izabrano iz skupine koja se sastoji od metanola, etanola, propanola, etil acetata, metil acetata, acetona i njihove smjese.
10. Postupak prema zahtjevu 1, naznačen time da se navedena klorovodična kiselina u koraku (4) koristi u količini od 3 do 10 mola ekvivalenata na osnovi 1 mol ekvivalenta spoja formule (IV).
11. Metoda prema zahtjevu 1, naznačena time što se korak (5) provodi u organskom otapalu odabranom iz skupine koja se sastoji od tetrahidrofurana, etil acetata, acetona, 1,4-dioksana, acetonitrila, diklorometana, tetraklorida ugljika, kloroforma, N, N -dimetil formamid i dimetilsulfoksid, ili mješavina navedenog organskog otapala i vode.
12. Postupak prema zahtjevu 1, naznačen time da je rečena baza u koraku (5) odabrana iz skupine koju čine natrijev karbonat, kalcijev karbonat, kalijev karbonat, natrijev hidroksid, kalijev hidroksid, ezijev karbonat, diizopropilamin, trietilamin, diizopropiletilamin i dietilamin.
13. Postupak prema zahtjevu 1, naznačen time, da se navedena baza u koraku (5) koristi u količini od 3 do 5 molnih ekvivalenata na osnovi 1 mol ekvivalenta spoja formule (III).
14. Postupak prema zahtjevu 1, naznačen time da korak (5) nadalje uključuje podvrgavanje spoja formule (II) rekristalizaciji vodenim acetonom u količini od 15 do 30 (w / v) puta, u odnosu na količinu spoja formule (III).
15. Postupak prema zahtjevu 1, naznačen time što se korak (6) provodi u organskom otapalu odabranom iz skupine koja se sastoji od metanola, etanola, propanola, izopropanola, butanola, etil acetata, acetona, tetrahidrofurana, acetonitrila, 1,4-dioksana i njihova smjesa.
16. N-(3,4-dikloro-2-fluorofenil)-7-metoksi-6-(piperidin-4-iloksi)kvinazolin-4-amin dihidroklorid formule (III):
[image]
17. tert-butil 4-(4-(3,4-dikloro-2-fluorofenilamino)-7-metoksikinazolin-6-iloksi)piperidin-1-karboksilat formule (IV):
[image]
18. 4-(3,4-dikloro-2-fluorofenilamino)-7-metoksikinazolin-6-ol formule (V):
[image]
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020110101422A KR101272613B1 (ko) | 2011-10-05 | 2011-10-05 | 1-(4-(4-(3,4-디클로로-2-플루오로페닐아미노)-7-메톡시퀴나졸린-6-일옥시)피페리딘-1-일)프로프-2-엔-1-온 염산염의 제조 방법 및 이에 사용되는 중간체 |
| PCT/KR2012/008077 WO2013051883A2 (en) | 2011-10-05 | 2012-10-05 | Method for preparing 1-(4-(4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)piperidin-1-yl)-prop-2-en-1-one hydrochloride and intermediates used therein |
| EP12838558.0A EP2763981B1 (en) | 2011-10-05 | 2012-10-05 | Method for preparing 1-(4-(4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)piperidin-1-yl)-prop-2-en-1-one hydrochloride and intermediates used therein |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20200426T1 true HRP20200426T1 (hr) | 2020-09-04 |
Family
ID=48044309
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20200426TT HRP20200426T1 (hr) | 2011-10-05 | 2012-10-05 | Postupak za pripremu 1-(4-(4-(3,4-dikloro-2-fluorofenilamino)-7-metoksikinazolin-6-iloksi)piperi din-1-il)-prop-2-en-1-on hidroklorida i posrednici koji se koriste |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US8859767B2 (hr) |
| EP (2) | EP2763981B1 (hr) |
| JP (1) | JP5805880B2 (hr) |
| KR (1) | KR101272613B1 (hr) |
| CN (2) | CN103857672B (hr) |
| AU (1) | AU2012319291B2 (hr) |
| BR (1) | BR112014007718B1 (hr) |
| CA (1) | CA2850055C (hr) |
| CY (1) | CY1122758T1 (hr) |
| DK (1) | DK2763981T3 (hr) |
| ES (1) | ES2775197T3 (hr) |
| HR (1) | HRP20200426T1 (hr) |
| HU (1) | HUE048798T2 (hr) |
| IL (3) | IL231911B (hr) |
| IN (1) | IN2014DN03447A (hr) |
| LT (1) | LT2763981T (hr) |
| MX (1) | MX348815B (hr) |
| PL (1) | PL2763981T3 (hr) |
| PT (1) | PT2763981T (hr) |
| RS (1) | RS60118B1 (hr) |
| RU (1) | RU2563630C1 (hr) |
| SI (1) | SI2763981T1 (hr) |
| WO (1) | WO2013051883A2 (hr) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101317809B1 (ko) | 2011-06-07 | 2013-10-16 | 한미약품 주식회사 | 암세포의 성장을 억제하는 아마이드 유도체 및 비금속염 활택제를 포함하는 약학 조성물 |
| KR20140096571A (ko) * | 2013-01-28 | 2014-08-06 | 한미약품 주식회사 | 1-(4-(4-(3,4-디클로로-2-플루오로페닐아미노)-7-메톡시퀴나졸린-6-일옥시)피페리딘-1-일)프로프-2-엔-1-온의 제조방법 |
| CN104513229A (zh) | 2013-09-28 | 2015-04-15 | 正大天晴药业集团股份有限公司 | 喹唑啉衍生物及其制备方法 |
| WO2016150340A1 (zh) | 2015-03-20 | 2016-09-29 | 正大天晴药业集团股份有限公司 | 喹唑啉衍生物的盐及其制备方法 |
| JP7554030B2 (ja) * | 2018-09-14 | 2024-09-19 | ハンミ ファーマシューティカル カンパニー リミテッド | キナゾリン化合物及びその塩酸塩の結晶形 |
| KR101950942B1 (ko) * | 2019-01-28 | 2019-02-22 | 한미약품 주식회사 | 1-(4-(4-(3,4-디클로로-2-플루오로페닐아미노)-7-메톡시퀴나졸린-6-일옥시)피페리딘-1-일)프로프-2-엔-1-온의 제조방법 |
| US20210221792A1 (en) * | 2020-01-16 | 2021-07-22 | Hanmi Pharm Co., Ltd. | Convergent synthesis of poziotinib derivative |
| WO2022043923A1 (en) * | 2020-08-28 | 2022-03-03 | Hanmi Science Co., Ltd. | Synthesis of poziotinib derivative |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200813014A (en) * | 2002-03-28 | 2008-03-16 | Astrazeneca Ab | Quinazoline derivatives |
| ATE353888T1 (de) * | 2003-09-19 | 2007-03-15 | Astrazeneca Ab | Chinazolinderivate |
| GB0322409D0 (en) * | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
| WO2007068552A1 (de) | 2005-12-12 | 2007-06-21 | Boehringer Ingelheim International Gmbh | Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| TWI377944B (en) * | 2007-06-05 | 2012-12-01 | Hanmi Holdings Co Ltd | Novel amide derivative for inhibiting the growth of cancer cells |
| MX2011011177A (es) * | 2009-04-23 | 2011-11-18 | Astrazeneca Ab | Proceso para la preparacion de 4-(3-cloro-2-fluoro-anilino)-7-meto xi-6-[1-(n-metilcarbamoilmetil) piperidin-4-il] quinazolina. |
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2011
- 2011-10-05 KR KR1020110101422A patent/KR101272613B1/ko not_active Expired - Fee Related
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2012
- 2012-10-05 RS RS20200295A patent/RS60118B1/sr unknown
- 2012-10-05 CN CN201280049302.7A patent/CN103857672B/zh active Active
- 2012-10-05 HR HRP20200426TT patent/HRP20200426T1/hr unknown
- 2012-10-05 LT LTEP12838558.0T patent/LT2763981T/lt unknown
- 2012-10-05 HU HUE12838558A patent/HUE048798T2/hu unknown
- 2012-10-05 CA CA2850055A patent/CA2850055C/en active Active
- 2012-10-05 EP EP12838558.0A patent/EP2763981B1/en active Active
- 2012-10-05 AU AU2012319291A patent/AU2012319291B2/en not_active Ceased
- 2012-10-05 BR BR112014007718-5A patent/BR112014007718B1/pt not_active IP Right Cessation
- 2012-10-05 JP JP2014534478A patent/JP5805880B2/ja not_active Expired - Fee Related
- 2012-10-05 DK DK12838558.0T patent/DK2763981T3/da active
- 2012-10-05 SI SI201231742T patent/SI2763981T1/sl unknown
- 2012-10-05 ES ES12838558T patent/ES2775197T3/es active Active
- 2012-10-05 RU RU2014117648/04A patent/RU2563630C1/ru active
- 2012-10-05 CN CN201811593540.XA patent/CN110003174A/zh active Pending
- 2012-10-05 EP EP19201644.2A patent/EP3611172A1/en not_active Withdrawn
- 2012-10-05 PL PL12838558T patent/PL2763981T3/pl unknown
- 2012-10-05 IN IN3447DEN2014 patent/IN2014DN03447A/en unknown
- 2012-10-05 MX MX2014003959A patent/MX348815B/es active IP Right Grant
- 2012-10-05 US US14/349,887 patent/US8859767B2/en active Active
- 2012-10-05 PT PT128385580T patent/PT2763981T/pt unknown
- 2012-10-05 WO PCT/KR2012/008077 patent/WO2013051883A2/en not_active Ceased
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- 2014-04-03 IL IL231911A patent/IL231911B/en active IP Right Grant
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- 2018-05-29 IL IL259694A patent/IL259694B/en unknown
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- 2020-03-11 CY CY20201100214T patent/CY1122758T1/el unknown
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2022
- 2022-03-27 IL IL291738A patent/IL291738A/en unknown
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