尿嘧啶(2)经1,3-二溴-5,5-二甲基乙内酰脲(DBH)溴代得5-溴尿嘧啶(3),收率由文献的86%提高至95%;3经五氯化磷氯化得2,4-二氯-5-溴嘧啶(4),革除了剧毒且刺激性强的三氯氧磷,收率由文献的88%提高至99%;4与环戊胺发生取代反应得5-溴-2-氯-N-环戊基嘧啶-4-胺(5);以氯化钯代替文献的乙酸钯作催化剂,5与巴豆酸经Heck反应后,再经内酰胺化成环得2-氯-8-环戊基-5-甲基吡啶并[2,3-d]嘧啶-7(8H)-酮(6),缩短了反应时间(由>36 h减少至6 h),收率也由80%提高至90%以上。6再经溴化、取代、Heck偶联、酸性水解以及脱保护反应制得帕博昔布(1),总收率52.1%(以2计)。 Uracil (2) was brominated with 1,3-dibromo-5,5-dimethylhydantoin (DBH) to give 5-bromouracil (3). The yield increased from 86% to 95% ; 3 chlorination of phosphorus pentachloride 2,4-dichloro-5-bromopyrimidine (4), get rid of the highly toxic and irritating phosphorus oxychloride, the yield increased from 88% of the literature to 99% ; 4 substituted with cyclopentylamine 5-bromo-2-chloro-N-cvclopentylpyrimidin-4-amine (5); with palladium chloride instead of literature palladium as a catalyst, 5 and crotonic acid via Heck After the reaction, 2-chloro-8-cyclopentyl-5-methylpyrido [2,3-d] pyrimidin- 7 (8H) -one (6) is cyclized by lactamization to shorten the reaction time From> 36 h to 6 h), the yield also increased from 80% to over 90%. 6 and then by bromination, substitution, Heck coupling, acidic hydrolysis and deprotection of the system to obtain the the irbesartan (1), the total yield of 52.1% (2).