AR077526A1 - Metodo para la sintesis de (1s,2r)- milnacipran - Google Patents
Metodo para la sintesis de (1s,2r)- milnacipranInfo
- Publication number
- AR077526A1 AR077526A1 ARP100100245A ARP100100245A AR077526A1 AR 077526 A1 AR077526 A1 AR 077526A1 AR P100100245 A ARP100100245 A AR P100100245A AR P100100245 A ARP100100245 A AR P100100245A AR 077526 A1 AR077526 A1 AR 077526A1
- Authority
- AR
- Argentina
- Prior art keywords
- formula
- reaction
- amide
- milnacipran
- phthalimide
- Prior art date
Links
- GJJFMKBJSRMPLA-DZGCQCFKSA-N levomilnacipran Chemical compound C=1C=CC=CC=1[C@]1(C(=O)N(CC)CC)C[C@H]1CN GJJFMKBJSRMPLA-DZGCQCFKSA-N 0.000 title abstract 4
- 238000000034 method Methods 0.000 title abstract 2
- 230000015572 biosynthetic process Effects 0.000 title 1
- 238000003786 synthesis reaction Methods 0.000 title 1
- 238000006243 chemical reaction Methods 0.000 abstract 4
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 abstract 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 abstract 3
- 239000002253 acid Substances 0.000 abstract 3
- 150000002596 lactones Chemical class 0.000 abstract 3
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical class C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 abstract 3
- RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 abstract 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 abstract 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 abstract 2
- 229910052783 alkali metal Inorganic materials 0.000 abstract 2
- 150000001340 alkali metals Chemical class 0.000 abstract 2
- 150000001408 amides Chemical class 0.000 abstract 2
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 abstract 2
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 abstract 2
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 abstract 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 abstract 2
- BRLQWZUYTZBJKN-VKHMYHEASA-N (-)-Epichlorohydrin Chemical compound ClC[C@H]1CO1 BRLQWZUYTZBJKN-VKHMYHEASA-N 0.000 abstract 1
- 238000010306 acid treatment Methods 0.000 abstract 1
- 150000001412 amines Chemical class 0.000 abstract 1
- 239000002585 base Substances 0.000 abstract 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 abstract 1
- XXBDWLFCJWSEKW-UHFFFAOYSA-N dimethylbenzylamine Chemical compound CN(C)CC1=CC=CC=C1 XXBDWLFCJWSEKW-UHFFFAOYSA-N 0.000 abstract 1
- 235000010299 hexamethylene tetramine Nutrition 0.000 abstract 1
- 239000004312 hexamethylene tetramine Substances 0.000 abstract 1
- 230000007062 hydrolysis Effects 0.000 abstract 1
- 238000006460 hydrolysis reaction Methods 0.000 abstract 1
- 125000005543 phthalimide group Chemical group 0.000 abstract 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 abstract 1
- -1 potassium salt Chemical class 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 239000002904 solvent Substances 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/16—Preparation of optical isomers
- C07C231/18—Preparation of optical isomers by stereospecific synthesis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C233/58—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Steroid Compounds (AREA)
Abstract
Reivindicacion 1: Un método para sintetizar una sal de adicion de ácido farmacéuticamente aceptable de (1S,2R)-milnaciprán de la formula (1), que comprende los siguientes pasos sucesivos: (a) reaccion de fenilacetonitrilo y de (R)-epiclorhidrina en presencia de una base que contiene un metal alcalino, seguida por un tratamiento básico, y luego por un tratamiento ácido para obtener la lactona de la formula (2); (b) reaccion de la lactona (2) obtenida en el paso (a) previo con MNEt2, en donde M representa un metal alcalino, o con NHEt2 en presencia de un complejo de ácido de Lewis-amina en donde la amina es seleccionada entre dietilamina, trietilamina, diisopropiletilamina, N,N-dietilanilina, N,N-dimetilbencilamina, N-metilpiperidina, N-metilmorfolina, N,N'-dimetilpiperazina y hexametilentetramina, para obtener el amida-alcohol de la formula (3; (c) reaccion del amida-alcohol de formula (3) obtenido en el paso (b) previo con cloruro de tionilo para obtener la amida clorada de la formula (4; (d) reaccion de la amida dorada de formula (4) obtenida en el paso (c) previo con una sal de ftalimida, tal como la sal de potasio, para obtener el derivado de ftalimida de la formula (5); (e) hidrolisis del grupo ftalimida del derivado de ftalimida de formula (5) obtenido en el paso (d) previo, para obtener (1S,2R)-milnaciprán, y (f) salificacion del (1S,2R)-milnaciprán obtenido en el paso (e) previo en un sistema adecuado de solventes, en presencia de un ácido farmacéuticamente aceptable.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0950552A FR2941454B1 (fr) | 2009-01-29 | 2009-01-29 | Proced de synthese du (1s,2r)-milnacipran |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR077526A1 true AR077526A1 (es) | 2011-09-07 |
Family
ID=40920574
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP100100245A AR077526A1 (es) | 2009-01-29 | 2010-01-29 | Metodo para la sintesis de (1s,2r)- milnacipran |
| ARP190101513A AR115475A2 (es) | 2009-01-29 | 2019-06-04 | Método para la síntesis de (1s,2r)-milnaciprán |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP190101513A AR115475A2 (es) | 2009-01-29 | 2019-06-04 | Método para la síntesis de (1s,2r)-milnaciprán |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US8604241B2 (es) |
| EP (1) | EP2391599B1 (es) |
| JP (1) | JP5646509B2 (es) |
| KR (1) | KR101719011B1 (es) |
| CN (2) | CN110204455A (es) |
| AR (2) | AR077526A1 (es) |
| AU (1) | AU2010209686B2 (es) |
| BR (1) | BRPI1007404B8 (es) |
| CA (1) | CA2750488C (es) |
| ES (1) | ES2472695T3 (es) |
| FR (1) | FR2941454B1 (es) |
| GE (1) | GEP20135903B (es) |
| IL (1) | IL214241A (es) |
| MA (1) | MA33025B1 (es) |
| MX (1) | MX2011007846A (es) |
| NZ (1) | NZ594291A (es) |
| PL (1) | PL2391599T3 (es) |
| RU (1) | RU2521342C2 (es) |
| TN (1) | TN2011000363A1 (es) |
| TW (1) | TWI455911B (es) |
| UA (1) | UA104884C2 (es) |
| WO (1) | WO2010086394A1 (es) |
| ZA (1) | ZA201105414B (es) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2944011B1 (fr) * | 2009-04-03 | 2011-05-20 | Pf Medicament | Derives d'aminocyclobutane ou d'aminocyclobutene, leur procede de preparation et leur utilisation a titre de medicaments. |
| WO2011158249A1 (en) * | 2010-06-16 | 2011-12-22 | Glenmark Generics Limited | Process for preparation of milnacipran intermediate and its use in preparation of pure milnacipran |
| WO2012046247A2 (en) * | 2010-10-06 | 2012-04-12 | Msn Laboratories Limited | Process for the preparation of (±m1r(s), 2srr)l-2-(aminomethyl)-n,n-diethyl-l-phenylcyclopropane carboxamide hydrochloride |
| ES2613709T3 (es) * | 2011-01-24 | 2017-05-25 | Bayer Intellectual Property Gmbh | Procedimiento para la preparación de 2,2-difluoroetilamina a partir de 2,2-difluoro-1-cloroetano |
| US9416109B2 (en) * | 2012-02-17 | 2016-08-16 | Eisai R&D Management Co., Ltd. | Methods and compounds useful in the synthesis of orexin-2 receptor antagonists |
| WO2014009767A1 (en) | 2012-07-07 | 2014-01-16 | Micro Labs Limited | An improved process for the preparation of 1-aryl 2-aminomethyl cyclopropane carboxyamide (z) derivatives, their isomers and salts |
| EP2805936A1 (en) | 2013-05-20 | 2014-11-26 | Cosma S.p.A. | Process for preparing levomilnacipran HCL |
| WO2014203277A2 (en) * | 2013-06-19 | 2014-12-24 | Msn Laboratories Private Limited | Process for the preparation of (1s,2r)-2-(aminomethyl)-n,n-diethyl-1-phenylcyclopropanearboxamide hydrochloride |
| CN103694162B (zh) * | 2014-01-03 | 2015-09-02 | 上海现代制药股份有限公司 | (1s,2r)-1-苯基2-(酞酰亚胺)甲基-n,n-二乙基-环丙甲酰胺的制备方法 |
| CN104058992A (zh) * | 2014-06-13 | 2014-09-24 | 上海现代制药股份有限公司 | 左旋米那普仑盐酸盐的晶型 |
| BR112017006115A2 (pt) | 2014-10-03 | 2017-12-19 | Purac Biochem Bv | método para a preparação de n,n-dialquilactamida |
| EP3230258B1 (en) | 2014-11-04 | 2019-06-26 | Química Sintética, S.A. | Process for the preparation of (1s,2r)-milnacipran |
| CN106083638A (zh) * | 2016-07-07 | 2016-11-09 | 佛山市隆信医药科技有限公司 | 一种盐酸左旋米那普仑的制备方法 |
| CN111175387B (zh) * | 2018-11-13 | 2022-06-07 | 成都康弘药业集团股份有限公司 | 一种米那普仑异构体的检测方法 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2508035A1 (fr) | 1981-06-23 | 1982-12-24 | Fabre Sa Pierre | Derives d'aryl-1-aminomethyl-2 cyclopropanes carboxamides (z), leur preparation et leur application en tant que medicaments utiles dans le traitement des troubles du systeme nerveux central |
| FR2581059B1 (fr) | 1985-04-25 | 1988-04-22 | Pf Medicament | Procede de preparation du chlorhydrate de phenyl-1 diethyl amino carbonyl-1 aminomethyl-2 cyclopropane (z) |
| FR2640972B1 (es) * | 1988-12-28 | 1991-04-19 | Pf Medicament | |
| WO1995022521A1 (en) | 1994-02-22 | 1995-08-24 | Asahi Kasei Kogyo Kabushiki Kaisha | Aminoalkylcyclopropane derivative |
| JPH0834765A (ja) * | 1994-02-22 | 1996-02-06 | Asahi Chem Ind Co Ltd | アミノアルキルシクロプロパン誘導体 |
| US7309799B2 (en) | 2004-06-01 | 2007-12-18 | Collegium Pharmaceutical, Inc. | Methods for the synthesis of milnacipran and congeners thereof |
| JP4712320B2 (ja) | 2004-06-16 | 2011-06-29 | 住友化学株式会社 | ２−オキソ−１−フェニル−３−オキサビシクロ［３．１．０］ヘキサンの製造方法 |
| JP4418717B2 (ja) * | 2004-06-24 | 2010-02-24 | 住友化学株式会社 | （ｚ）−１−フェニル−１−ジエチルアミノカルボニル−２−アミノメチルシクロプロパン塩酸塩の製造方法 |
| CN100579954C (zh) | 2004-06-25 | 2010-01-13 | 住友化学株式会社 | (z)-1-苯基-1-二乙氨基羰基-2-羟甲基环丙烷的制造方法 |
| JP4828863B2 (ja) | 2005-01-28 | 2011-11-30 | 住友化学株式会社 | （ｚ）−１−フェニル−１−（ｎ，ｎ−ジエチルアミノカルボニル）−２−フタルイミドメチルシクロプロパンの製造方法 |
| KR100772244B1 (ko) * | 2005-07-20 | 2007-11-01 | 안국약품 주식회사 | 밀나시프란염산염의 제조방법 |
| CN102986288B (zh) | 2009-12-04 | 2016-12-07 | 交互数字专利控股公司 | 用于混合网络中的汇聚网关的扩展本地ip接入 |
-
2009
- 2009-01-29 FR FR0950552A patent/FR2941454B1/fr active Active
-
2010
- 2010-01-25 TW TW099101933A patent/TWI455911B/zh active
- 2010-01-29 WO PCT/EP2010/051045 patent/WO2010086394A1/en not_active Ceased
- 2010-01-29 AU AU2010209686A patent/AU2010209686B2/en active Active
- 2010-01-29 JP JP2011546850A patent/JP5646509B2/ja active Active
- 2010-01-29 NZ NZ594291A patent/NZ594291A/xx unknown
- 2010-01-29 MX MX2011007846A patent/MX2011007846A/es active IP Right Grant
- 2010-01-29 MA MA34052A patent/MA33025B1/fr unknown
- 2010-01-29 AR ARP100100245A patent/AR077526A1/es not_active Application Discontinuation
- 2010-01-29 CN CN201910530393.XA patent/CN110204455A/zh active Pending
- 2010-01-29 CN CN2010800057211A patent/CN102300840A/zh active Pending
- 2010-01-29 BR BRPI1007404A patent/BRPI1007404B8/pt active IP Right Grant
- 2010-01-29 ES ES10701538.0T patent/ES2472695T3/es active Active
- 2010-01-29 CA CA2750488A patent/CA2750488C/en active Active
- 2010-01-29 RU RU2011135326/04A patent/RU2521342C2/ru active
- 2010-01-29 GE GEAP201012350A patent/GEP20135903B/en unknown
- 2010-01-29 KR KR1020117019602A patent/KR101719011B1/ko active Active
- 2010-01-29 EP EP10701538.0A patent/EP2391599B1/en active Active
- 2010-01-29 PL PL10701538T patent/PL2391599T3/pl unknown
- 2010-01-29 UA UAA201110404A patent/UA104884C2/uk unknown
- 2010-01-29 US US13/146,361 patent/US8604241B2/en active Active
-
2011
- 2011-07-21 IL IL214241A patent/IL214241A/en active IP Right Grant
- 2011-07-22 TN TN2011000363A patent/TN2011000363A1/fr unknown
- 2011-07-22 ZA ZA2011/05414A patent/ZA201105414B/en unknown
-
2019
- 2019-06-04 AR ARP190101513A patent/AR115475A2/es active IP Right Grant
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