JQ1合成工艺的改进
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摘要
目的改进JQ1的合成工艺。方法以4-氯苯甲酰基乙腈为原料,与丁酮和硫在碱性条件下环合得到中间体Ⅴ[(2-氨基-4,5-二甲基噻吩-3-基)(4-氯苯基)甲酮];中间体Ⅴ再与9-芴甲氧羰基-天冬氨酸-β-叔丁基酯成酰胺后,脱保护得到中间体Ⅲ[(S)-3-氨基4-((3-(4-氯苯甲酰基)-4,5-二甲基噻吩-2-基)氨基)-4-氧丁酸叔丁酯],后者经环合、构建三唑环,得到目标化合物JQ1。结果与结论通过1HNMR、13CNMR、MS及IR对目标产物进行了结构确证,HPLC检测其纯度达100%;以原料4-氯苯甲酰基乙腈计算,产物的总收率为21.2%。
OBJECTIVE To improve the synthesis process of JQ1. METHODS 3-(4-chlorophenyl)-3-oxopropanenitrile was used as the starting material. And its product of cyclization with butanone and sulphur were adopted as the intermediate Ⅴ. Ⅴ was acylated by 4-tert-butyl N-fmoc-L-aspartate and then deprotected to give intermediate Ⅲ. JQ1 was gained through two cyclization reactions of Ⅲ. RESULTS and CONCLUSION The structure of JQ1 was confirmed by1 HNMR,13 CNMR,MS and IR. JQ1 had successfully been synthesized with a total yield of 21. 2% based on 3-(4-chlorophenyl)-3-oxopropanenitrile and a purity of 100%.
OBJECTIVE To improve the synthesis process of JQ1. METHODS 3-(4-chlorophenyl)-3-oxopropanenitrile was used as the starting material. And its product of cyclization with butanone and sulphur were adopted as the intermediate Ⅴ. Ⅴ was acylated by 4-tert-butyl N-fmoc-L-aspartate and then deprotected to give intermediate Ⅲ. JQ1 was gained through two cyclization reactions of Ⅲ. RESULTS and CONCLUSION The structure of JQ1 was confirmed by1 HNMR,13 CNMR,MS and IR. JQ1 had successfully been synthesized with a total yield of 21. 2% based on 3-(4-chlorophenyl)-3-oxopropanenitrile and a purity of 100%.
引文
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