HRP20150700T1 - Postupak za pripravu bifenil-2-il karbaminske kiseline - Google Patents
Postupak za pripravu bifenil-2-il karbaminske kiseline Download PDFInfo
- Publication number
- HRP20150700T1 HRP20150700T1 HRP20150700TT HRP20150700T HRP20150700T1 HR P20150700 T1 HRP20150700 T1 HR P20150700T1 HR P20150700T T HRP20150700T T HR P20150700TT HR P20150700 T HRP20150700 T HR P20150700T HR P20150700 T1 HRP20150700 T1 HR P20150700T1
- Authority
- HR
- Croatia
- Prior art keywords
- formula
- compound
- image
- carried out
- isolating
- Prior art date
Links
- QMOVGVNKXUTCQU-UHFFFAOYSA-N (2-phenylphenyl)carbamic acid Chemical compound OC(=O)NC1=CC=CC=C1C1=CC=CC=C1 QMOVGVNKXUTCQU-UHFFFAOYSA-N 0.000 title 1
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 18
- 238000000034 method Methods 0.000 claims 15
- 239000003638 chemical reducing agent Substances 0.000 claims 5
- 239000012458 free base Substances 0.000 claims 4
- 239000007787 solid Substances 0.000 claims 4
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims 3
- -1 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)- 4 methylmorpholinium compound Chemical class 0.000 claims 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- 230000008878 coupling Effects 0.000 claims 3
- 238000010168 coupling process Methods 0.000 claims 3
- 238000005859 coupling reaction Methods 0.000 claims 3
- 239000011541 reaction mixture Substances 0.000 claims 3
- 238000006268 reductive amination reaction Methods 0.000 claims 3
- 239000003153 chemical reaction reagent Substances 0.000 claims 2
- 239000013078 crystal Substances 0.000 claims 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 claims 2
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 238000010533 azeotropic distillation Methods 0.000 claims 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 claims 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims 1
- 238000006264 debenzylation reaction Methods 0.000 claims 1
- 238000010511 deprotection reaction Methods 0.000 claims 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims 1
- 229940011051 isopropyl acetate Drugs 0.000 claims 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
Classifications
-
- 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
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (12)
1. Postupak za pripravu kristalne slobodne baze (Oblik III) spoja formule I:
[image]
naznačen time, da se postupak sastoji od sljedećih koraka:
(a) spajanja spoja formule 8:
[image]
u nazočnosti reagensa za spajanje kako bi se dobio spoj formule 10:
[image]
(b) reduktivne aminacije spoja formule 10 i spoja formule 11:
[image]
u nazočnosti sredstva za redukciju kako bi se dobio spoj formule I, pri čemu se azeotropna destilacija vode izvodi pri povišenoj temperaturi prije dodavanja redukcijskog sredstva, a reduktivna aminacija se izvodi pri sobnoj temperaturi;
(c) dovođenja u dodir proizvoda iz koaraka (b) s izopropil acetatom, po potrebi, dodavanjem sjemena kristala kristalne slobodne baze (Oblik III) kako bi se oblikovala krutina, te izdvajanja dobivene krutine; i
(d) dovođenja u dodir proizvoda iz koraka (c) s toluenom, po potrebi, dodavanje, sjemena kristala kristalne slobodne baze (Oblik III) kako bi se oblikovala krutina, te izdvajanja dobivene krutine kao kristalne slobodne baze (Oblik III); gdje se korak (a) i korak (b) izvode u istoj reakcijskoj smjesi bez izdvajanja intermedijera iz koraka (a).
2. Postupak u skladu s patentnim zahtjevom 1, naznačen time, da se korak (a) izvodi u metiltetrahidrofuranu.
3. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 2, naznačen time, da je reagens za spajanje u koraku (a) 4-(4,6-dimetoksi-1,3,5-triazin-2-il)-4 metilmorfolinium spoj.
4. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačen time, da je povišena temperatura u koraku (b) unutar raspona od oko 40-70°C.
5. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time, da je redukcijsko sredstvo iz koraka (b) natrijev triacetoksiborohidrid.
6. Postupak u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačen time, da je spoj formule 8 dobiven postupkom koji se sastoji od sljedećih koraka:
(e) redukcijske aminacije spoja formule 3:
[image]
i spoja formule 6:
[image]
u nazočnosti redukcijskog sredstva, kako bi se dobio spoj formule 7:
[image]
i
(f) debenzilacije spoja formule 7 kako bi se dobio spoj formule 8; pri čemu se korak (e) i korak (f) izvode u istoj reakcijskoj smjesi bez izdvajanja intermedijera iz koraka (e).
7. Postupak u skladu s patentnim zahtjevom 6, naznačen time, da se koraci (e) i (f) izvode u metiltetrahidrofuranu.
8. Postupak u skladu s bilo kojim od patentnih zahtjeva 6 do 7, naznačen time, da je redukcijsko sredstvo iz koraka (e) natrijev triacetoksiborohidrid.
9. Postupak u skladu s bilo kojim od patentnih zahtjeva 6 do 8, naznačen time, da je spoj formule 3 dobiven postupkom koji se sastoji od sljedećih koraka:
(i) karbobenziloksi zaštita spoja formule 1:
[image]
gdje je svaki R neovisno C1-6alkil ili su uzeti zajedno kako bi oblikovali dioksan ili dioksolan, čime se dobiva spoj formule 2:
[image]
i
(ii) uklanjanja zaštite acetala spoja formule 2, čime se dobiva spoj formule 3.
10. Postupak u skladu s patentnim zahtjevom 9, naznačen time, da se korak (ii) i korak (e) izvode u istoj reakcijskoj smjesi bez izdvajanja intermedijera iz koraka (ii).
11. Postupak u skladu s patentnim zahtjevom 9, naznačen time, da se izvodi u metiltetrahidrofuranu.
12. Postupak u skladu s patentnim zahtjevom 9, naznačen time, da korak (i) obuhvaća kombiniranje spoja formule 1 i benzil kloroformata.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36372510P | 2010-07-13 | 2010-07-13 | |
| PCT/US2011/042530 WO2012009166A1 (en) | 2010-07-13 | 2011-06-30 | Process for preparing a biphenyl-2-ylcarbamic acid |
| EP11734208.9A EP2593429B1 (en) | 2010-07-13 | 2011-06-30 | Process for preparing a biphenyl-2-ylcarbamic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20150700T1 true HRP20150700T1 (hr) | 2015-08-14 |
Family
ID=44514976
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20150700TT HRP20150700T1 (hr) | 2010-07-13 | 2015-06-30 | Postupak za pripravu bifenil-2-il karbaminske kiseline |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US8754225B2 (hr) |
| EP (1) | EP2593429B1 (hr) |
| JP (2) | JP5959117B2 (hr) |
| KR (1) | KR101742253B1 (hr) |
| CN (1) | CN102958916B (hr) |
| AU (1) | AU2011279602B2 (hr) |
| BR (1) | BR112013000877B1 (hr) |
| CA (1) | CA2801101C (hr) |
| DK (1) | DK2593429T3 (hr) |
| ES (1) | ES2544287T3 (hr) |
| HK (1) | HK1184145A1 (hr) |
| HR (1) | HRP20150700T1 (hr) |
| HU (1) | HUE027140T2 (hr) |
| IL (1) | IL223328A (hr) |
| MX (1) | MX2013000456A (hr) |
| PL (1) | PL2593429T3 (hr) |
| PT (1) | PT2593429E (hr) |
| RS (1) | RS54201B1 (hr) |
| SG (1) | SG186708A1 (hr) |
| SI (1) | SI2593429T1 (hr) |
| SM (1) | SMT201500204B (hr) |
| WO (1) | WO2012009166A1 (hr) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI341836B (en) | 2004-03-11 | 2011-05-11 | Theravance Inc | Biphenyl compounds useful as muscarinic receptor antagonists |
| MX2012000682A (es) | 2009-07-15 | 2012-02-28 | Theravance Inc | Formas de bases libres cristalinas de un compuesto de bifenilo. |
| US11484531B2 (en) | 2018-08-30 | 2022-11-01 | Theravance Biopharma R&D Ip, Llc | Methods for treating chronic obstructive pulmonary disease |
| CN110526859B (zh) * | 2019-08-07 | 2021-03-12 | 山东百诺医药股份有限公司 | 一种瑞维那新中间体及其制备方法和瑞维那新的制备方法 |
| WO2022049604A1 (en) * | 2020-09-05 | 2022-03-10 | Cipla Limited | Process for preparing revefenacin and intermediates therof |
| CN112694434B (zh) * | 2020-12-29 | 2023-06-16 | 浙江和泽医药科技股份有限公司 | 一种雷芬那辛新中间体及其活性亲电砌块和雷芬那辛的新制备方法 |
| CN113121412A (zh) * | 2021-04-20 | 2021-07-16 | 扬州中宝药业股份有限公司 | 一种雷芬那辛中间体的制备方法 |
| US20240327352A1 (en) * | 2021-07-17 | 2024-10-03 | Msn Laboratories Private Ltd, R&D Center | Novel process for the preparation of 1-(2-{4-[(4-carbamoylpiperidin-1-yl)methyl]- n-methylbenzamido}ethyl)piperidin-4-yl n-({1,1'-biphenyl}-2-yl)carbamate |
| KR102700997B1 (ko) * | 2021-09-15 | 2024-08-30 | (주)부흥산업사 | (2S, 5R)-벤질-5-(t-부톡시카르보닐아미노)-2-메틸피페리딘-1-카르복실레이트의 제조방법 |
| CN118401497A (zh) | 2021-12-09 | 2024-07-26 | 医药化学公司 | 雷芬那辛的结晶型丙酮溶剂化物 |
| CN114276290B (zh) * | 2021-12-24 | 2024-05-28 | 浙江和泽医药科技股份有限公司 | 一种雷芬那辛无水晶型及其制备方法 |
| CN115093365B (zh) * | 2022-07-25 | 2023-07-25 | 沈阳药科大学 | 一种雷芬那辛的合成方法 |
| CN116514704B (zh) * | 2023-07-01 | 2023-09-29 | 北京远大九和药业有限公司 | 一种雷芬那辛中间体及其制备方法 |
| CN117263848A (zh) * | 2023-09-19 | 2023-12-22 | 山东京卫制药有限公司 | 一种雷芬那辛的吸入喷雾剂 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6816878B1 (en) * | 2000-02-11 | 2004-11-09 | Steven L. Zimmers | Alert notification system |
| PE20040950A1 (es) * | 2003-02-14 | 2005-01-01 | Theravance Inc | DERIVADOS DE BIFENILO COMO AGONISTAS DE LOS RECEPTORES ADRENERGICOS ß2 Y COMO ANTAGONISTAS DE LOS RECEPTORES MUSCARINICOS |
| US7228657B2 (en) | 2003-07-10 | 2007-06-12 | Controlled Environments Limited | Climate control for a greenhouse |
| ES2329586T3 (es) * | 2003-11-21 | 2009-11-27 | Theravance, Inc. | Compuestos que tienen actividad agonista del receptor beta2 adrenergico y antagonista del receptor muscarino. |
| TWI341836B (en) | 2004-03-11 | 2011-05-11 | Theravance Inc | Biphenyl compounds useful as muscarinic receptor antagonists |
| US7659403B2 (en) * | 2005-03-10 | 2010-02-09 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| TWI372749B (en) * | 2005-03-10 | 2012-09-21 | Theravance Inc | Crystalline forms of a biphenyl compound |
| MX2012000682A (es) * | 2009-07-15 | 2012-02-28 | Theravance Inc | Formas de bases libres cristalinas de un compuesto de bifenilo. |
-
2011
- 2011-06-30 SG SG2012090858A patent/SG186708A1/en unknown
- 2011-06-30 PT PT117342089T patent/PT2593429E/pt unknown
- 2011-06-30 SI SI201130576T patent/SI2593429T1/sl unknown
- 2011-06-30 PL PL11734208T patent/PL2593429T3/pl unknown
- 2011-06-30 CN CN201180030278.8A patent/CN102958916B/zh active Active
- 2011-06-30 RS RS20150524A patent/RS54201B1/en unknown
- 2011-06-30 EP EP11734208.9A patent/EP2593429B1/en active Active
- 2011-06-30 MX MX2013000456A patent/MX2013000456A/es active IP Right Grant
- 2011-06-30 AU AU2011279602A patent/AU2011279602B2/en active Active
- 2011-06-30 BR BR112013000877-6A patent/BR112013000877B1/pt active IP Right Grant
- 2011-06-30 WO PCT/US2011/042530 patent/WO2012009166A1/en active Application Filing
- 2011-06-30 ES ES11734208.9T patent/ES2544287T3/es active Active
- 2011-06-30 JP JP2013519700A patent/JP5959117B2/ja active Active
- 2011-06-30 US US13/173,274 patent/US8754225B2/en active Active
- 2011-06-30 CA CA2801101A patent/CA2801101C/en active Active
- 2011-06-30 HU HUE11734208A patent/HUE027140T2/hu unknown
- 2011-06-30 KR KR1020137003526A patent/KR101742253B1/ko active IP Right Grant
- 2011-06-30 DK DK11734208.9T patent/DK2593429T3/en active
-
2012
- 2012-11-28 IL IL223328A patent/IL223328A/en active IP Right Grant
-
2013
- 2013-10-15 HK HK13111590.6A patent/HK1184145A1/xx unknown
- 2013-11-26 US US14/090,211 patent/US9035061B2/en active Active
-
2015
- 2015-04-03 JP JP2015076528A patent/JP2015127342A/ja active Pending
- 2015-06-30 HR HRP20150700TT patent/HRP20150700T1/hr unknown
- 2015-08-28 SM SM201500204T patent/SMT201500204B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2011279602A1 (en) | 2013-02-21 |
| SMT201500204B (it) | 2015-10-30 |
| SI2593429T1 (sl) | 2015-10-30 |
| JP5959117B2 (ja) | 2016-08-02 |
| IL223328A (en) | 2015-07-30 |
| CN102958916A (zh) | 2013-03-06 |
| KR20130129177A (ko) | 2013-11-27 |
| ES2544287T3 (es) | 2015-08-28 |
| US9035061B2 (en) | 2015-05-19 |
| EP2593429B1 (en) | 2015-06-03 |
| US8754225B2 (en) | 2014-06-17 |
| RS54201B1 (en) | 2015-12-31 |
| AU2011279602B2 (en) | 2015-04-09 |
| SG186708A1 (en) | 2013-02-28 |
| JP2015127342A (ja) | 2015-07-09 |
| KR101742253B1 (ko) | 2017-05-31 |
| CN102958916B (zh) | 2015-03-25 |
| HK1184145A1 (en) | 2014-01-17 |
| JP2013532631A (ja) | 2013-08-19 |
| PL2593429T3 (pl) | 2015-10-30 |
| US20120016130A1 (en) | 2012-01-19 |
| IL223328A0 (en) | 2013-02-03 |
| EP2593429A1 (en) | 2013-05-22 |
| HUE027140T2 (hu) | 2016-08-29 |
| BR112013000877A2 (pt) | 2016-05-17 |
| BR112013000877B1 (pt) | 2021-07-06 |
| PT2593429E (pt) | 2015-09-24 |
| MX2013000456A (es) | 2013-02-27 |
| US20140121378A1 (en) | 2014-05-01 |
| WO2012009166A1 (en) | 2012-01-19 |
| DK2593429T3 (en) | 2015-09-07 |
| CA2801101C (en) | 2018-01-16 |
| CA2801101A1 (en) | 2012-01-19 |
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