RDEA3170合成工艺优化

Synthetic process optimization of RDEA3170

摘要:

利用1,4-二溴萘为起始原料，经溴-镁交换反应、4-溴-1-萘甲酰胺的合成和脱水，得到了一条新的4-溴-1-萘甲腈合成路线。通过连续反应法，以一种催化剂Pd(PPh3)2Cl2实现了4-溴-1-萘甲腈的Miyaura硼烷基化及其与2-((3-溴吡啶-4-基)硫)-2-甲基丙酸乙酯的Suzuki偶联。对偶联反应的最佳条件及产物水解生成RDEA3170的条件进行了优化。该合成路线RDEA3170的总收率达到42%，适合工业化生产。

Abstract:

4-bromo-1-naphthonitrile was obtained by a new route of bromo-magnesium exchanging reaction, synthesis and dehydration of 4-bromo-1-naphthamide using 1,4-dibromonaphthalene as starting materials. The Miyaura borylation of 4-bromine-1- naphthonitrile and its Suzuki coupling with ethyl 2-(3-bromopyridine-4-yl)thio-2-methylpropionate were realized using Pd(PPh3)2Cl2 as catalyst by a continuous reaction method. The conditions for coupling reaction and the hydrolysis of the product to produce RDEA3170 were optimized. The overall yield of RDEA3170 is 42% and the optimized synthetic process is suitable for the industrial production.