西酞普兰有关物质的合成

Synthesis of citalopram related substances

目的设计、合成西酞普兰原料药有关物质作为其质量研究过程中的参照物。方法分别以西酞普兰为起始原料,经氧化反应、脱甲基反应和氮氧化反应合成西酞普兰有关物质:1-(3-(二甲基氨基)丙基)-1-(4-氟苯基)-1,3-二氢-5-羧酰胺基异苯并呋喃(A)、1-(4-氟苯基)-1-(3-(甲基氨基)丙基)-1,3-二氢-5-氰基异苯并呋喃(D)、1-[3-(二甲氨基)丙基]-1-(4-氟苯基)-1,3-二氢-5-氰基异苯并呋喃N-氧化物(E);以西酞普兰合成工艺中的化合物4为起始原料经琼斯试剂氧化、氢化合成西酞普兰有关物质:1-(3-(二甲基氨基)丙基)-1-(4-氟苯基)-3-氧代-1,3-二氢-5-氰基异苯并呋喃(B)、1-(3-(二甲基氨基)丙基)-1-(4-氟苯基)-3-羟基-1,3-二氢-5-氰基异苯并呋喃(C)。结果合成了5种西酞普兰有关物质,其结构经;H-NMR,^(13)C-NMR和ESI-MS谱确证。结论西酞普兰有关物质的合成研究对其原料药质量研究方面具有重要意义。

The research of citalopram related substances is of great significance to the quality research of its API(active pharmaceutical ingredient) technology.In this paper, five related substances of citalopram were synthesized, namely 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carboxamide(A),1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-3-hydroxy-1,3-dihydroisobenzofuran-5-carbonitrile(B),1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-3-oxo-1,3-dihydroisobenzofuran-5-carbonitrile(C),1-(4-fluorophenyl)-1-(3-(methylamino)propyl)-1,3-dihydroisobenzofuran-5-carbonitrile(D),3-(5-cyano-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)-N,N-dimethylpropan-1-amine oxide(E).And the experimental steps and key control parameters were described in detail.The structures were confirmed by;H-NMR,^(13)C-NMR and ESI-MS.These compounds would be used as the references for the quality control of citalopram API.