来曲唑的制备

Preparation of letrozole

本文研究了抗癌药物来曲唑的三步合成法。第一步:在醇类溶剂中,20℃以下,4,4’-二氰基二苯甲酮经硼氢化钠还原生成4,4’-二氰基二苯甲醇;第二步:在非极性溶剂中,4,4’-二氰基二苯甲醇经氯代反应生成4,4’-二氰基二苯基氯甲烷;第三步:在混合溶剂中,80℃左右,4,4’-二氰基二苯基氯甲烷与1,2,4-三氮唑缩合反应生成来曲唑,总产率大于50%,质量符合USP30标准,且该工艺操作简便、安全,原料成本低,适合于来曲唑的工艺化大生产。

SThrough three steps to synthesize anticancer drug letrozole were studied.First,in the alcohol solvent,below 20 ℃,through sodium borohydride reduction of bis-(4-cyanphenyl)-ketone to bis-(4-cyanphenyl)-methanol ;Second Step;in the non-polar solvent,through chlorination of bis-(4-cyanphenyl)-methanol to chloro-bis-(4-cyanophenyl)-methane;Finally;in the mixed solvent,about 80 ℃,through condensation of chloro-bis-(4-cyanophenyl)-methane and 1,2,4-triazole to letrozole.The gross production rate is more than 50%,in line with USP30 quality standards,the process is simple,safe,low cost of raw materials and suitable for the process of large-scale production.