C5a受体拮抗剂W-54011的合成

Synthesis of C5a Receptor Antagonist W-54011

以7-甲氧基-1-萘满酮为原料,经Wittig反应、去甲基化、烯醇互变和Jones氧化反应等制得关键中间体7-甲氧基-1,2,3,4-四氢化萘-1-羧酸(4);4-异丙基苯胺和4-(二甲基胺基)苯甲醛经过还原胺化反应得(E)-4-{[(4-异丙基苯基)亚胺基]甲基}-N,N-二甲基苯胺(6);4转化为相应的酰氯后与6反应合成N-[4-(二甲基氨基)苄基]-N-(4-异丙基苯基)-7-甲氧基-1,2,3,4-四氢化萘-1-甲酰胺(W-54011),总收率24%,其结构经1H NMR,13C NMR和HR-MS(ESI)表征。

Using 7-methoxy-1-tetralinone as a raw material,7-methoxy-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid(4)was obtained by series of reactions including Wittig reaction,demethylation,enol interconversion and Jones oxidation.(E)-4-(4-(4-isopropylphenyl)imido)-N,N-dimethylaniline(6)was synthesized by the reductive amination reaction of 4-(dimethylamino)benzaldehyde with 4-isopropylaniline.N-(4-(dimethylamino)benzyl)-N-(4-isopropylphenyl)-7-methoxy-1,2,3,4-tetrahydronaphthalene-1-carboxamide(W-54011)was synthesized by 6 with acyl chloride which was converted from 4,the overall yield was 24%.The structures were characterized by 1H NMR,13C NMR and HR-MS(ESI).