甲磺酸达比加群酯有关物质的合成

发布时间：2018-09-19 18:41

【摘要】：根据甲磺酸达比加群酯的结构特征和合成工艺,制备了可能的10种有关物质:4-[[(己氧基)羰基]脒基]苯胺(A)、2-[[[4-(氨基亚甲胺基)苯基]氨基]甲基]-1-甲基-1H-苯并咪唑-5-羧酸乙酯(B)、2-[[[4-[[(己氧基)羰基]-氨基亚甲胺基]苯基]氨基]甲基]-1-甲基-1H-苯并咪唑-5-羧酸乙酯(C)、3-[[[2-[[[4-[[(己氧基)羰基]氨基亚甲胺基]-苯基]氨基]甲基]-1-甲基-1H-苯并咪唑-5-基]羰基](吡啶-2-基)氨基]丙酸甲酯(D)、3-[[[2-[[[4-[[[(己氧基)羰基]氨基]羰基]苯基]氨基]甲基]-1-甲基-1H-苯并咪唑-5-基]羰基](吡啶-2-基)氨基]丙酸甲酯(E)、3-[[[2-[[[4-(氨基亚甲胺基)苯基]氨基]甲基]-1-甲基-1H-苯并咪唑-5-基]羰基](吡啶-2-基)氨基]丙酸(F)、3-[[[2-[[[4-[[(己氧基)羰基]氨基亚甲胺基]苯基]氨基]甲基]-1-甲基-1H-苯并咪唑-5-基]羰基](吡啶-2-基)-氨基]丙酸(G)、3-[[[2-[[[4-[[(己氧基)羰基]氨基亚甲胺基]苯基]氨基]甲基]-1-甲基-1H-苯并咪唑-5-基]羰基](吡啶-2-基)氨基]丙酰胺(H)、3-[[[2-[[[4-[[[(己氧基)羰基]氨基]羰基]苯基]氨基]甲基]-1-甲基-1H-苯并咪唑-5-基]羰基](吡啶-2-基)氨基]丙酸乙酯(I)和3-[[[2-[[[4-[[[(己氧基)羰基]氨基]羰基]苯基]氨基]-甲基]-1-甲基-1H-苯并咪唑-5-基]羰基](吡啶-2-基)氨基]丙酸(J),并经1H NMR和MS确证结构,以作为甲磺酸达比加群酯质量研究的参照物。
[Abstract]:According to the structural characteristics and synthesis process of dapi group ester of methanesulfonic acid, Ten possible related substances, 1: 4- [(hexoxy) carbonyl] amidine] aniline (A) 2- [4- (aminomethylamino) phenyl] amino] methyl] -1-methyl-1H-benzimidazole-5-carboxylate ethyl ester (B) _ 2- [4- [(hexoxy) carbonyl] -aminomethylamino] benzene were prepared. Ethyl (C) 3- [2- [4- [hexoxy carbonyl] aminomethyl] methyl] -1-methyl-1H-benzimidazolyl] carbonyl] (pyridine-2-yl) amino] methyl propionate 3- [2- [4- [4- [4- [4- [4-] 4- [(hexoxy) carbonyl] aminomethylamino] methyl] -1-methyl-1H-benzimidazole-5-] carbonyl] (pyridin-2-yl) amino acid methyl ester (D) 3- [4- [4- [4- [(hexoxy) carbonyl] aminomethyl] methyl group] Hexoxy) carbonyl] amino] phenyl] amino] methyl] -1-methyl-1H-benzimidazole-5-yl] carbonyl] (pyridine-2-yl) amino] propionate methyl ester (E) 3- [2- [4- (aminomethylamino) phenyl] amino] methyl] -1-methyl-1H-benzomido] methyl (F) 3- [2- [4- [(hexoxy) carbonyl] aminomethyl] methyl] -1-methyl-1H-benzimidazolyl] carbonyl] (pyridin-2-yl) -amino] propionate (G) 3- [2- [4- [hexoxy) carbonyl] phenyl] amino] methyl-1-methyl-1H-benzimidazolyl] carbonyl] (pyridin-2-yl) -amino] propionate 3- [2- [4- [(hexoxy) carbonyl] methyl] -1-methyl-1H-benzimidazole-5-] carbonyl] (pyridine-2-yl) -amino] propionic acid Methyl] -1-methyl-1H-benzimidazole-5-yl] carbonyl] (pyridine-2-yl) amino] propionamide (H) 3- [2- [4- [(hexoxy) carbonyl] amino] carbonyl] phenyl] methyl] -1-methyl-1H-benzo (pyridine-2-yl) amino] propionamide 3- [2- [4- [hexoxy carbonyl] amino] carbonyl] phenyl] amino] methyl] -1-methyl-1H-benzoyl] (I) and 3- [2- [4- [(hexoxy) carbonyl] amino] phenyl] amino] -methyl] -1-methyl-1H-benzimidazolyl] carbonyl] (pyridin-2-yl) amino] propionate (J), The structure was confirmed by 1H NMR and MS. It is used as a reference material for the quality study of dapi-group ester of methanesulfonic acid.
【作者单位】：中国医药工业研究总院上海医药工业研究院创新药物与制药工艺国家重点实验室;
【分类号】：R914.5

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