Novel synthetic method of Palbociclib

Abstract

The invention provides a novel synthetic method of Palbociclib, comprising the following steps: 1) under the action of alkali and a solvent, an intermediate V and an intermediate B1 undergo a condensation reaction to obtain a compound VI; 2) the compound VI undergoes exchange with a Grignard reagent, and then the exchange reaction product reacts with an acylation reagent to obtain a compound VII; when X is acetyl, the compound VI is the compound VII; 3) the compound VII undergoes deprotection reaction under the action of hydroxyethanesulphonic acid and finally salification is conducted so as to obtain the finished product Palbociclib X. the synthetic method has a simple process route, is low-cost, and is suitable for industrial production. The synthetic route is as shown 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 palbociclib. Background technique [0002] Palbocicib (trade name Ibrance) is a new type of high-efficiency oral anticancer drug developed by Pfizer. It is the first CDK4 / 6 kinase inhibitor on the market in the world, which can selectively inhibit cyclin-dependent kinases 4 and 6, and has a remarkable effect in the treatment of advanced breast cancer. The global breast cancer drug market can reach tens of billions of dollars each year, and palbociclib has a broad market prospect. [0003] Palbociclib chemical name: 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2, 3-d] pyrimidin-7-one isethionate, the molecular structure is as follows: [0004] [0005] In the current synthesis methods reported in the literature, the molecular structure skeleton of the product is generally formed by the dockin...

AI Technical Summary

Problems solved by technology

[0015] The process uses methyl 2-acetylbutyrate, malononitrile and guanidine derivatives for one-pot cyclization to obtain the skeleton molecule of the product. Although the reaction steps are shortened, the ring-closing, diazotization, amidoalkyl There are many side reactions in the radicalization and oxidation reactions, not only the scale-up operation is difficult, the reaction yield is low, but also the product purification is difficult, which is not conducive to process scale-up, so it is still necessary to find a new synthesis method that is simpler, more efficient, and lower cost

Images