(alpha-甲基苯乙基)(1-甲基-2-苯氧基乙基)富马酸氢铵

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (alpha-甲基苯乙基)(1-甲基-2-苯氧基乙基)富马酸氢铵
• 英文名称: (E)-4-hydroxy-4-oxobut-2-enoate;1-phenoxypropan-2-yl(1-phenylpropan-2-yl)azanium
• 化学式: C22H27NO5
• 分子量: 385.5
• InChiKey: PVNHTDOWUIYZFC-WLHGVMLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.03
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

文献信息

• PROCESS FOR THE PRODUCTION OF RALFINAMIDE SALTS SUBSTANTIALLY FREE FROM IMPURITIES HAVING GENOTOXIC EFFECTS
  申请人：Giordano Claudio

  公开号：US20130039983A1

  公开（公告）日：2013-02-14

  The invention relates to a new process for the production and/or purification of the salt of the compound (S)-2-[4-(2-fluorobenzyloxy)benzylamino]propanamide, i.e. ralfinamide, or the respective R-enantiomer, with methanesulfonic acid in high yields and very high enantiomeric and chemical purity in the form of the crystalline anhydrous polymorph identified as form A, wherein said salt is substantially free from impurities having genotoxic effect, such as (C 1 -C 5 )alkanylmethanesulfonates, and residual solvents known as potential precursors thereof, such as (C 1 -C 5 )alkanols or esters thereof with lower alkanoic acids. The process foresees (i) production and/or crystallization of the salt, from water, acetone, an aliphatic ketone of 4-5 carbon, atoms or mixtures thereof with water, or (ii) slurring the solid salt with (a) water, (b) a mixture of water with acetone or an aliphatic ketone of 4-5 carbon atoms, (c) acetone, an aliphatic ketone of 4-5 carbon atoms or a mixture thereof, or (iii) exposure of the solid salt to air stream having high degree of relative humidity, and, when the obtained product consists as a whole or in part of crystalline hemihydrate pseudopolymorph form H crystals, converting said product into anhydrous form A crystals by submitting it to water removal. The crystalline hemihydrate pseudopolymorph form H of ralfinamide methanesulfonate, or its R-enantiomer, is a useful intermediate for obtaining the crystalline anhydrous polymorph A free from the above impurities having genotoxic effect and/or residual solvents known as precursors thereof, and exhibits a physicochemical profile conferring significant advantages in the design and development of solid dosage forms, in particular, of modified release formulations.

  本发明涉及一种新的工艺，用于制备和/或纯化化合物(S)-2-[4-(2-氟苯甲氧基)苯基氨基]丙酰胺的盐，即拉尔非那酰胺，或其相应的R-对映体，使用甲烷磺酸，在高产率和非常高的对映体和化学纯度下以晶体无水多形式式A的形式制备，其中该盐基本上不含对基因毒性有影响的杂质，例如(C1-C5)烷基甲磺酸盐，以及已知的潜在前体的残留溶剂，例如(C1-C5)烷醇或其与较低的烷基酸酯的混合物。该工艺预见(i)从水，丙酮，4-5个碳原子的脂肪酮或其与水的混合物中制备和/或结晶盐，或(ii)用(a)水，(b)水与丙酮或4-5个碳原子的脂肪酮的混合物，(c)丙酮，4-5个碳原子的脂肪酮或其混合物混合物泥浆化固体盐，或(iii)将固体盐暴露于具有高相对湿度的空气流中，当所得产品整体或部分由晶体半水合物伪多形式式H晶体组成时，通过将其提交给水去除，将所得产品转化为无水形式A晶体。拉尔非那甲磺酸盐的晶体半水合物伪多形式式H，或其R-对映体，是获得无上述基因毒性影响和/或已知前体的残留溶剂的晶体无水多形式式A的有用中间体，并展示出物理化学特性，在固体剂量制剂的设计和开发中具有重要优势，特别是在改性释放制剂中。
• Process for the production of ralfinamide methanesulfonate salts or their R-enantiomers
  申请人：Newron Pharmaceuticals S.p.A.

  公开号：EP2563355B1

  公开（公告）日：2016-06-08
• PROCESS FOR THE PRODUCTION OF RALFINAMIDE METHANESULFONATE SALTS OR THEIR R-ENANTIOMERS
  申请人：Newron Pharmaceuticals S.p.A.

  公开号：EP2563355A1

  公开（公告）日：2013-03-06
• US9505708B2
  申请人：——

  公开号：US9505708B2

  公开（公告）日：2016-11-29
• US9856207B2
  申请人：——

  公开号：US9856207B2

  公开（公告）日：2018-01-02