New synthesis method of ribociclib intermediate

Abstract

The invention discloses preparation of a ribociclib key intermediate A; propiolic acid ester or amide 2 is directly used as a Sonogashira coupling side chain, coupling conditions are optimized, an intermediate 3 is obtained with relatively high yield, the intermediate 3 is directly subjected to ring closing under simple conditions to complete construction of a mother ring molecule, to obtain a structural formula A or a precursor ester 4 of the structural formula A, and the precursor ester 4 is subjected to hydrolysis and condensation to obtain the structural formula A. The route has simple operation, reaction steps are shorted, the yield is relatively high, and the purity of the obtained product is relatively high, and the method is suitable for enlarged production, wherein the reaction route is described in the specification.

Description

technical field

[0001] The invention belongs to the field of medicine and chemical industry, and relates to a new synthesis method for preparing an intermediate compound of Ribociclib. Background technique

[0002] Ribociclib is a new type of high-efficiency oral anti-cancer drug developed by Novartis. It is a highly specific cell cycle-dependent kinase (CDK4 / 6 dual inhibitor), which can significantly inhibit the growth of a variety of neuroblastomas, and is used for the treatment of advanced breast cancer. Recent clinical research results have shown that the efficacy is significant, so it has broad application market expectation.

[0003] Ribociclib chemical name: 7-cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)-piperidin-2-yl]amino}-7H-pyrrole[ The structure of 2,3-d] pyrimidine-6-carboxamide is shown below. In the synthesis methods reported in the literature, the key reaction is how to quickly prepare the key intermediate parent ring molecule A.

[0004]

[0005] P...

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