JP2013519650A - リバロキサバンの調製方法 - Google Patents
リバロキサバンの調製方法 Download PDFInfo
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- JP2013519650A JP2013519650A JP2012552389A JP2012552389A JP2013519650A JP 2013519650 A JP2013519650 A JP 2013519650A JP 2012552389 A JP2012552389 A JP 2012552389A JP 2012552389 A JP2012552389 A JP 2012552389A JP 2013519650 A JP2013519650 A JP 2013519650A
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- pseudohalogen
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- 0 *c1ccc(C(NCC(COS(=O)=O)O)=O)[s]1 Chemical compound *c1ccc(C(NCC(COS(=O)=O)O)=O)[s]1 0.000 description 9
- OZDHTNDEOLAQAW-AWEZNQCLSA-N Cc1ccc(C(NC[C@@H](CN2c(cc3)ccc3NC(CO)=O)OC2=O)=O)[s]1 Chemical compound Cc1ccc(C(NC[C@@H](CN2c(cc3)ccc3NC(CO)=O)OC2=O)=O)[s]1 OZDHTNDEOLAQAW-AWEZNQCLSA-N 0.000 description 2
- QIYLXCXKWRXSAJ-UHFFFAOYSA-N C=C=CNc1ccc(C(N=CC(COS(=O)=O)O)=O)[s]1 Chemical compound C=C=CNc1ccc(C(N=CC(COS(=O)=O)O)=O)[s]1 QIYLXCXKWRXSAJ-UHFFFAOYSA-N 0.000 description 1
- OOSRMHLLXNEGRJ-CQSZACIVSA-N C=C=Nc1ccc(C(NC[C@@H](CNc(cc2)ccc2NC(CO)=O)O)=O)[s]1 Chemical compound C=C=Nc1ccc(C(NC[C@@H](CNc(cc2)ccc2NC(CO)=O)O)=O)[s]1 OOSRMHLLXNEGRJ-CQSZACIVSA-N 0.000 description 1
- GTHQXNIEPWGIMQ-UHFFFAOYSA-N Nc(cc1)ccc1NC(CO)=O Chemical compound Nc(cc1)ccc1NC(CO)=O GTHQXNIEPWGIMQ-UHFFFAOYSA-N 0.000 description 1
- VIXKPVMGNGIDKP-UHFFFAOYSA-N OCC(Nc(cc1)ccc1N=C=O)=O Chemical compound OCC(Nc(cc1)ccc1N=C=O)=O VIXKPVMGNGIDKP-UHFFFAOYSA-N 0.000 description 1
- JNAFWZOLBIGOCD-HNNXBMFYSA-N O[C@@H](CCNC(c([s]1)ccc1Cl)=O)CNc(cc1)ccc1N(CCOC1)C1=O Chemical compound O[C@@H](CCNC(c([s]1)ccc1Cl)=O)CNc(cc1)ccc1N(CCOC1)C1=O JNAFWZOLBIGOCD-HNNXBMFYSA-N 0.000 description 1
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Classifications
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- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D413/12—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 chain containing hetero atoms as chain links
Abstract
Description
式(I)を有する化合物の例は周知である。これらの化合物は、WO2004/060887に開示されている方法に類似する慣用的な方法によって調製することができる。例えば、(2S)−3−アミノプロパン−1,2−ジオールを、塩基性条件下で、5−ハロゲノチオフェン−2−カルボニルハライドと反応させることができる。
式(II)を有する化合物を、まず、無水酢酸と反応させて、式(II)を有する化合物の対応するアセチル誘導体を得ることができる。アシル化反応は、典型的には、プロトン性または非プロトン性溶媒中で行われる。適切な溶媒の例は、(塩化メチレンのような)ハロゲン化炭化水素、(トルエンのような)炭化水素、(DMFのような)アミド、(スルホランのような)スルホン、(ピリジンのような)芳香族塩基、(イソプロパノールのような)アルコールおよびこれらの混合物を含む。
式(II)を有する化合物のアセチル誘導体を式(VIII)を有する化合物と反応させて、式(V)を有する化合物を得ることができる。
4−[4−[(5R)−5−(クロロチオフェノ−2−カルボン酸((S)−2,3−ジヒドロキシ−プロピル)−アミド
4−[4−[(5R)−5−(クロロチオフェノ−2−カルボン酸((S)−2−ヒドロキシ−3−トシルオキシ)−プロピル)−アミド
1H−NMR(DMSO−d6,300Mz)δ(ppm)=2.29(s,CH3,3H)、3.10−3.25(m,CH2N,2H)、3.74−3.87(m,CH,CH2,2H)、3.98(dd,CH2,1H,J10.2Hz,J3.2Hz)、7.17(d,CH,1H,J4.0Hz)、7.42(d,CH,1H,J9.1Hz)、7.58(d,CH,1H,J4.0Hz)、7.75(d,CH,1H,J9.1Hz)、8.58(t.NH,1H,J5.8Hz)。
4−[4−[(5R)−5−(クロロチオフェノ−2−カルボン酸((S)−2−ヒドロキシ−3−トシルオキシ)−プロピル)−アミド
5−クロロチオフェン−2−カルボン酸−{(R)−2−ヒドロキシ−3−[4−(3−オキソモルホリン−4−イル)フェニルアミノ]プロピル}アミド
5−クロロ−N−({(5S)−2−オキソ−3−[4−(3−オキソ−4−モルホリニル)フェニル]−1,3−オキサゾリジン−5−イル}メチル)−2−チオフェンカルボキサミド
トルエン−4−スルホン酸(S)−3−[(5−クロロ−チオフェン−2−カルボニル)−アミノ]−2−[4−(3−オキソ−モルホリン−4−イル)−フェニルカルバモイルオキシ]−プロピルエステル
1H−NMR(DMSO−d6,300Mz)δ(ppm)=2.29(s,CH3,3H)、3.49(m,CH2N,2H)、3.68(m,CH2,2H)、3.95(m,CH2,2H)、4.18(s,CH2CO,2H)、4.18−4.32(m,CH2,2H)、5.07(m,CH,1H)、7.18(d,J=1.9Hz,CH,1H)、7.22−7.48(m,CH,6H)、7.59(d,J=3.9Hz,CH,1H)、7.77(d,J=1.9Hz,CH,1H)、8.75(t.J5.1Hz,NH,1H)、9.81(s,NH,1H)。
5−クロロ−N−({(5S)−2−オキソ−3−[4−(3−オキソ−4−モルホリニル)フェニル]−1,3−オキサゾリン−5−イル}メチル)−2−チオフェンカルボキサミド
4−(イソシアナート−フェニル)−モルホリン−3−オン
1H−NMR(CD3CN,300Mz)δ(ppm)=3.71(m,CH2O,2H)、3.00(m,CH2N,2H)、3.92(m,CH2,2H)、4.21(s,CH2CO,2H)、7.21 and 7.37(m,CH,4H)。
5−クロロ−N−({(5S)−2−オキソ−3−[4−(3−オキソ−4−モルホリニル)フェニル]−1,3−オキサゾリジン−5−イル}メチル)−2−チオフェンカルボキサミド
5−クロロ−チオフェン−2−カルボン酸((S)−1−オキシラニルメチル)−アミド
5−クロロ−N−({(5S)−2−オキソ−3−[4−(3−オキソ−4−モルホリニル)フェニル]−1,3−オキサゾリジン−5−イル}メチル)−2−チオフェンカルボキサミド
[4−(3−オキソ−モルホリン−4−イル)−フェニル]−カルバミン酸ベンジルエステル
Claims (15)
- R1がメチル、フェニルおよびトリルから選択される、請求項1に記載の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP10153160.6 | 2010-02-10 | ||
EP10153160A EP2354128A1 (en) | 2010-02-10 | 2010-02-10 | Method for the preparation of rivaroxaban |
PCT/EP2011/051920 WO2011098501A1 (en) | 2010-02-10 | 2011-02-10 | Method for the preparation of rivaroxaban |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2013519650A true JP2013519650A (ja) | 2013-05-30 |
JP5274725B2 JP5274725B2 (ja) | 2013-08-28 |
Family
ID=42355383
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012552389A Active JP5274725B2 (ja) | 2010-02-10 | 2011-02-10 | リバロキサバンの調製方法 |
Country Status (9)
Country | Link |
---|---|
US (1) | US8648189B2 (ja) |
EP (2) | EP2354128A1 (ja) |
JP (1) | JP5274725B2 (ja) |
CN (1) | CN102753537B (ja) |
AU (1) | AU2011214423B2 (ja) |
BR (1) | BR112012019936A2 (ja) |
CA (1) | CA2788755C (ja) |
RU (1) | RU2012138259A (ja) |
WO (1) | WO2011098501A1 (ja) |
Families Citing this family (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2404920A1 (en) | 2010-07-06 | 2012-01-11 | Sandoz AG | Crystalline form of Rivaroxaban dihydrate |
CN102584738B (zh) * | 2011-01-07 | 2015-04-29 | 浙江九洲药业股份有限公司 | 一种合成利伐沙班中间体的工艺 |
CN103254148B (zh) | 2012-02-15 | 2016-04-13 | 浙江海正药业股份有限公司 | 利奈唑胺中间体的制备方法 |
CZ2012111A3 (cs) | 2012-02-16 | 2013-08-28 | Zentiva, K.S. | Zpusob prípravy rivaroxabanu zalozený na vyuzití (S)-epichlorhydrinu |
CN103288814B (zh) | 2012-02-24 | 2016-07-06 | 国药集团国瑞药业有限公司 | 一种利伐沙班中间体的制备方法 |
JP2015514114A (ja) | 2012-04-06 | 2015-05-18 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションIndiana University Research And Technology Corporation | リバーロキサバンを調製するためのプロセス |
EP2838897A1 (en) | 2012-04-16 | 2015-02-25 | Ranbaxy Laboratories Limited | Process for the preparation of rivaroxaban and intermediates thereof |
US9376427B2 (en) | 2012-05-02 | 2016-06-28 | Symed Labs Limited | Process for preparing rivaroxaban using intermediates |
SG11201407518SA (en) * | 2012-05-24 | 2014-12-30 | Ranbaxy Lab Ltd | Process for the preparation of rivaroxaban |
CN102702186B (zh) * | 2012-06-20 | 2014-11-19 | 安润医药科技(苏州)有限公司 | 利伐沙班的合成方法 |
WO2014049552A2 (en) * | 2012-09-26 | 2014-04-03 | Ranbaxy Laboratories Limited | Process for the preparation of rivaroxaban |
WO2014102822A2 (en) | 2012-12-26 | 2014-07-03 | Wanbury Ltd. | Aldehyde derivative of substitute oxazolidinones |
HUE032850T2 (en) | 2012-12-26 | 2017-11-28 | Wanbury Ltd | Rivaroxaban intermediate and its preparation |
WO2014155259A2 (en) | 2013-03-25 | 2014-10-02 | Glenmark Pharmaceuticals Limited; Glenmark Generics Limited | Process for the preparation of rivaroxaban |
CN104098556B (zh) * | 2013-04-09 | 2019-01-08 | 浙江九洲药物科技有限公司 | 一种利伐沙班的合成工艺 |
CN104109158A (zh) * | 2013-04-16 | 2014-10-22 | 上海医药工业研究院 | 一种纯化利伐沙班的方法 |
CN103351385A (zh) * | 2013-06-28 | 2013-10-16 | 浙江燎原药业有限公司 | 一种利伐沙班中间体的制备方法 |
CN103819468A (zh) * | 2013-12-05 | 2014-05-28 | 浙江天宇药业股份有限公司 | 一种利伐沙班及其中间体的合成方法 |
ES2723355T3 (es) | 2013-12-06 | 2019-08-26 | Eisai R&D Man Co Ltd | Métodos útiles en la síntesis de análogos de halicondrina B |
IN2014MU00072A (ja) | 2014-01-08 | 2015-08-21 | Wockhardt Ltd | |
IN2014CH00290A (ja) | 2014-01-23 | 2015-08-14 | Symed Labs Ltd | |
CN105085371B (zh) * | 2014-04-22 | 2017-06-16 | 北大方正集团有限公司 | (s)‑{1‑(氯甲酸酯基)‑2‑[2‑(1,3‑二氧异吲哚)基]乙基}卤化盐及其制备方法 |
CN105085507B (zh) * | 2014-04-22 | 2017-11-24 | 北大方正集团有限公司 | 一种合成利伐沙班的方法 |
CN105085508B (zh) * | 2014-04-22 | 2017-12-08 | 北大方正集团有限公司 | 一种合成利伐沙班关键中间体的方法 |
CN105085370B (zh) * | 2014-04-22 | 2017-04-12 | 北大方正集团有限公司 | (s)‑1‑卤代‑2‑[2‑(1,3‑二氧异吲哚)基]乙基氯甲酸酯及其制备方法 |
CN105566310A (zh) * | 2014-10-15 | 2016-05-11 | 常州诺贝朗生物医药科技有限公司 | 一种利伐沙班中间体的制备方法 |
CN106588905A (zh) * | 2016-12-13 | 2017-04-26 | 重庆英斯凯化工有限公司 | 一种利伐沙班中间体的制备方法 |
CN112500403B (zh) * | 2020-12-28 | 2022-04-05 | 南京法恩化学有限公司 | 一种利伐沙班的制备方法 |
Citations (3)
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JP2003519141A (ja) * | 1999-12-24 | 2003-06-17 | バイエル アクチェンゲゼルシャフト | 置換オキサゾリジノン及び血液凝固の分野におけるそれらの使用 |
JP2006528943A (ja) * | 2003-05-19 | 2006-12-28 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | 複素環式化合物 |
JP2009514822A (ja) * | 2005-11-02 | 2009-04-09 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | フェニレン−ビス−オキサゾリジン誘導体およびそれらの使用 |
Family Cites Families (4)
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GB9318641D0 (en) * | 1993-09-08 | 1993-10-27 | Edko Trading Representation | Compositions |
FR2841997B1 (fr) | 2002-07-08 | 2005-11-11 | Gemplus Card Int | Securisation d'application telechargee notamment dans une carte a puce |
DE10300111A1 (de) * | 2003-01-07 | 2004-07-15 | Bayer Healthcare Ag | Verfahren zur Herstellung von 5-Chlor-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)-phenyl]-1,3-oxazolidin-5-yl}-methyl)-2-thiophencarboxamid |
CN1772750A (zh) * | 2005-11-15 | 2006-05-17 | 郑州大学 | (r)-n-(3-氟-4-吗啉苯基)-噁唑酮-5-甲基醇制备工艺 |
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2010
- 2010-02-10 EP EP10153160A patent/EP2354128A1/en not_active Ceased
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2011
- 2011-02-10 CN CN201180009134.4A patent/CN102753537B/zh active Active
- 2011-02-10 CA CA2788755A patent/CA2788755C/en not_active Expired - Fee Related
- 2011-02-10 WO PCT/EP2011/051920 patent/WO2011098501A1/en active Application Filing
- 2011-02-10 US US13/577,441 patent/US8648189B2/en active Active
- 2011-02-10 AU AU2011214423A patent/AU2011214423B2/en active Active
- 2011-02-10 JP JP2012552389A patent/JP5274725B2/ja active Active
- 2011-02-10 BR BR112012019936A patent/BR112012019936A2/pt not_active IP Right Cessation
- 2011-02-10 RU RU2012138259/04A patent/RU2012138259A/ru not_active Application Discontinuation
- 2011-02-10 EP EP11702646.8A patent/EP2521717B1/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003519141A (ja) * | 1999-12-24 | 2003-06-17 | バイエル アクチェンゲゼルシャフト | 置換オキサゾリジノン及び血液凝固の分野におけるそれらの使用 |
JP2006528943A (ja) * | 2003-05-19 | 2006-12-28 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | 複素環式化合物 |
JP2009514822A (ja) * | 2005-11-02 | 2009-04-09 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | フェニレン−ビス−オキサゾリジン誘導体およびそれらの使用 |
Also Published As
Publication number | Publication date |
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EP2521717B1 (en) | 2013-05-22 |
AU2011214423B2 (en) | 2015-06-11 |
BR112012019936A2 (pt) | 2015-09-22 |
EP2354128A1 (en) | 2011-08-10 |
CA2788755A1 (en) | 2011-08-18 |
EP2521717A1 (en) | 2012-11-14 |
US8648189B2 (en) | 2014-02-11 |
JP5274725B2 (ja) | 2013-08-28 |
CN102753537A (zh) | 2012-10-24 |
RU2012138259A (ru) | 2014-03-20 |
AU2011214423A1 (en) | 2012-08-30 |
CA2788755C (en) | 2015-03-31 |
US20130184457A1 (en) | 2013-07-18 |
WO2011098501A1 (en) | 2011-08-18 |
CN102753537B (zh) | 2015-09-02 |
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Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |