[EN] PROCESS FOR THE PREPARATION OF BARICITINIB AND AN INTERMEDIATE THEREOF<br/>[FR] PROCÉDÉ DE SYNTHÈSE DE BARICITINIB ET D'UN INTERMÉDIAIRE DE CELUI-CI
申请人:SUN PHARMACEUTICAL IND LTD
公开号:WO2016088094A1
公开(公告)日:2016-06-09
The present invention provides a process for the preparation of baricitinib and an intermediate thereof. The present invention provides a convenient, economical, and industrially advantageous two-step process for the preparation of [4-(IH-pyrazol-4-yl)-7Hpyrrolo[2,3-d] pyrimidin-7-yl]methyl pivalate of Formula (II). The process of the present invention involves the use of an alkali or alkaline earth metal hydroxide, carbonate, or bicarbonate as a base for reacting 4-chloro-7H-pyrrolo[2,3-d]pyrimidine of Formula (III) with chloromethyl pivalate of Formula (IV), and the use of an unprotected pyrazole borolane of Formula (VIII) for the conversion of (4-chloro-7H-pyrrolo[2,3-d] pynmidin-7- yl)methyl 2,2-dimethylpropanoate of Formula V into [4-(1 H-pyrazol-4-yl)-7Hpyrrolo[2,3-d]pyrimidin-7-yl]methyl pivalate of Formula (II). The process of the present invention provides [4-(1 H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl pivalate of Formula (I) in high yield.
本发明提供了一种用于制备巴瑞替尼及其中间体的方法。本发明提供了一种方便、经济和工业上有优势的两步法制备[4-(1H-吡唑-4-基)-7H-吡咯并[2,3-d]嘧啶-7-基]甲基季戊酸酯的方法。本发明的方法涉及使用碱金属或碱土金属的氢氧化物、碳酸盐或碳酸氢盐作为碱基,将化合物III的4-氯-7H-吡咯并[2,3-d]嘧啶与化合物IV的氯甲基季戊酸酯反应,以及使用未保护的吡唑硼杂环己烷化合物VIII将化合物V的(4-氯-7H-吡咯并[2,3-d]嘧啶-7-基)甲基-2,2-二甲基丙酸酯转化为[4-(1H-吡唑-4-基)-7H-吡咯并[2,3-d]嘧啶-7-基]甲基季戊酸酯的方法。本发明的方法以高产率提供了化合物I的[4-(1H-吡唑-4-基)-7H-吡咯并[2,3-d]嘧啶-7-基]甲基季戊酸酯。