摘要
2,4-二氟苯甲酸经碘代、酰化及缩合反应制得2-(2,4-二氟-5-碘苯甲酰基)-3-二甲胺基丙烯酸乙酯,再与L-缬氨醇发生加成消除反应、环合、叔丁基二甲基氯硅烷保护羟基制得[(S)-1-叔丁基二甲基硅氧甲基-2-甲基丙基]-7-氟-6-碘-4-氧代-1,4-二氢喹啉-3-甲酸乙酯,与3-氯-2-氟苄锌溴发生Negishi偶联反应后经"一锅煮"(脱保护、水解和甲氧基化反应)制得抗HIV药物埃替格韦,总收率约42%。
Elvitegravir was synthesized from 2,4-diftuorobenzoic acid via iodization, acylation and condensation to give ethyl 2- (2,4-difluoro-5-iodobenzoyl) -3-dimethylaminoacrylate, which was subjected to addition-elimination with L-valinol, cyclization, protection with tert-butyldimethylsilyl chloride and Negishi coupling reaction with 3-chloro-2- fluorobenzylzinc bromide, followed by one-pot synthesis including deprotection, hydrolysis and methoxylation with an overall yield of about 42 %.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2014年第1期5-8,共4页
Chinese Journal of Pharmaceuticals
关键词
埃替格韦
抗病毒药
喹诺酮
合成
elvitegravir
antivirus agent
quinolone
synthesis