HUE030504T2 - Process for the preparation of ralfinamide methanesulfonate salts or their R-enantiomers - Google Patents
Process for the preparation of ralfinamide methanesulfonate salts or their R-enantiomers Download PDFInfo
- Publication number
- HUE030504T2 HUE030504T2 HUE11714958A HUE11714958A HUE030504T2 HU E030504 T2 HUE030504 T2 HU E030504T2 HU E11714958 A HUE11714958 A HU E11714958A HU E11714958 A HUE11714958 A HU E11714958A HU E030504 T2 HUE030504 T2 HU E030504T2
- Authority
- HU
- Hungary
- Prior art keywords
- water
- crystalline
- salt
- mixture
- methanesulfonate
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 123
- -1 ralfinamide methanesulfonate salts Chemical class 0.000 title claims description 60
- 230000008569 process Effects 0.000 title claims description 55
- 238000004519 manufacturing process Methods 0.000 title description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 280
- BHJIBOFHEFDSAU-LBPRGKRZSA-N ralfinamide Chemical compound C1=CC(CN[C@@H](C)C(N)=O)=CC=C1OCC1=CC=CC=C1F BHJIBOFHEFDSAU-LBPRGKRZSA-N 0.000 claims description 165
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 161
- 239000000203 mixture Substances 0.000 claims description 159
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 148
- 150000003839 salts Chemical class 0.000 claims description 140
- 239000013557 residual solvent Substances 0.000 claims description 90
- 239000012535 impurity Substances 0.000 claims description 89
- 239000002904 solvent Substances 0.000 claims description 87
- 239000013078 crystal Substances 0.000 claims description 83
- 239000000243 solution Substances 0.000 claims description 82
- 230000001738 genotoxic effect Effects 0.000 claims description 73
- 231100000024 genotoxic Toxicity 0.000 claims description 72
- 238000002425 crystallisation Methods 0.000 claims description 69
- 230000008025 crystallization Effects 0.000 claims description 69
- 239000007787 solid Substances 0.000 claims description 65
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 64
- 239000002243 precursor Substances 0.000 claims description 61
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 52
- PLUBXMRUUVWRLT-UHFFFAOYSA-N Ethyl methanesulfonate Chemical compound CCOS(C)(=O)=O PLUBXMRUUVWRLT-UHFFFAOYSA-N 0.000 claims description 49
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 47
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 claims description 47
- 238000004458 analytical method Methods 0.000 claims description 46
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 claims description 46
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 claims description 45
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims description 42
- 230000015572 biosynthetic process Effects 0.000 claims description 38
- 239000012458 free base Substances 0.000 claims description 36
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- 125000000217 alkyl group Chemical group 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
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- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical class N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 claims 2
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- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 63
- 238000004128 high performance liquid chromatography Methods 0.000 description 56
- SWWHCQCMVCPLEQ-UHFFFAOYSA-N propan-2-yl methanesulfonate Chemical class CC(C)OS(C)(=O)=O SWWHCQCMVCPLEQ-UHFFFAOYSA-N 0.000 description 49
- CHQVNINIGBRKGZ-YDALLXLXSA-N (2s)-2-[[4-[(2-fluorophenyl)methoxy]phenyl]methylamino]propanamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=CC(CN[C@@H](C)C(N)=O)=CC=C1OCC1=CC=CC=C1F CHQVNINIGBRKGZ-YDALLXLXSA-N 0.000 description 39
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- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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| CN103804341B (zh) * | 2012-11-13 | 2018-04-10 | 中国人民解放军军事医学科学院毒物药物研究所 | 酰胺衍生物及其医药用途 |
| CN104761531B (zh) * | 2014-01-03 | 2017-12-01 | 中国人民解放军军事医学科学院毒物药物研究所 | 镇痛活性化合物及其医药用途 |
| CN104292128A (zh) * | 2014-07-01 | 2015-01-21 | 南京正科制药有限公司 | 一种沙芬酰胺晶型a |
| CN115368310B (zh) | 2021-05-18 | 2025-06-27 | 奥库菲尔医药公司 | 合成甲磺酸酚妥拉明的方法 |
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| IL94466A (en) | 1989-05-25 | 1995-01-24 | Erba Carlo Spa | Pharmaceutical preparations containing the history of A-amino carboxamide N-phenylalkyl are converted into such new compounds and their preparation |
| GB9515412D0 (en) * | 1995-07-27 | 1995-09-27 | Pharmacia Spa | 2-(4-substituted)-benzylamino-2-methyl-propanamide derivatives |
| GB9727523D0 (en) | 1997-12-31 | 1998-02-25 | Pharmacia & Upjohn Spa | Alpha-aminoamide derivatives useful as analgesic agents |
| CN1274306C (zh) | 2001-09-03 | 2006-09-13 | 纽朗制药有限公司 | 包含加巴喷丁或其类似物和α－氨基酰胺的药物组合物及其止痛应用 |
| EP1438956A1 (en) | 2003-01-16 | 2004-07-21 | Newron Pharmaceuticals S.p.A. | Alpha-aminoamide derivatives useful as antimigraine agents |
| CA2514574A1 (en) * | 2003-01-30 | 2004-08-12 | Dynogen Pharmaceuticals, Inc. | Use of sodium channel modulators for treating gastrointestinal tract disorders |
| AR044007A1 (es) | 2003-04-11 | 2005-08-24 | Newron Pharmaceuticals Inc | Metodos para el tratamiento de la enfermedad de parkinson |
| US20070276046A1 (en) | 2003-08-25 | 2007-11-29 | Patricia Salvati | Alpha-Aminoamide Derivatives Useful as Anti-Inflammatory Agents |
| EP1557166A1 (en) | 2004-01-21 | 2005-07-27 | Newron Pharmaceuticals S.p.A. | Alpha-aminoamide derivatives useful in the treatment of lower urinary tract disorders |
| EP1588704A1 (en) | 2004-04-22 | 2005-10-26 | Newron Pharmaceuticals S.p.A. | Alpha-aminoamide derivatives useful in the treatment of restless legs syndrome and addictive disorders |
| RS51411B (sr) * | 2004-09-10 | 2011-02-28 | Newron Pharmaceuticals S.P.A. | Upotreba (r)-(halobenziloksi) benzilamino-propanamida kao selektivnih modulatora natrijumovih i/ili kalcijumovih kanala |
| EP1870097A1 (en) | 2006-06-15 | 2007-12-26 | Newron Pharmaceuticals S.p.A. | Alpha-aminoamide derivatives useful in the treatment of cognitive disorders |
| KR101491541B1 (ko) * | 2006-06-19 | 2015-02-09 | 뉴론 파마슈티칼즈 에스. 피. 에이. | 2-［4-(3- 및 2-플루오로벤질옥시)벤질아미노)프로판 아미드의 제조방법 |
| JP5315674B2 (ja) * | 2007-11-19 | 2013-10-16 | セントラル硝子株式会社 | 非水電池用電解液及びこれを用いた非水電池 |
| EP3257842B1 (en) * | 2007-12-11 | 2020-11-18 | Newron Pharmaceuticals S.p.A. | Therapeutic use of 2-[4-(3- or 2-fluorobenzyloxy)benzylamino]propanamides with high purity degree |
| CN101903021B (zh) | 2007-12-19 | 2012-11-14 | 纽朗制药有限公司 | 用于治疗精神病的α-氨基酰胺衍生物 |
| WO2009109334A1 (en) | 2008-03-07 | 2009-09-11 | Newron Pharmaceuticals S.P.A. | (s)-(+)-2-[4-fluorbenzyloxy)benzylamino]propanamide for use in the treatment of mixed or combined pain |
| LT2563355T (lt) * | 2010-04-27 | 2016-09-26 | Newron Pharmaceuticals S.P.A. | Ralfinamido metansulfonato druskų arba jų r-enentiomerų gavimo būdas |
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