Method for preparing CDK4/6 inhibitor key intermediate through chemical-enzymatic method

An enzymatic preparation and inhibitor technology, applied in organic chemistry, fermentation, etc., can solve the problems of high cost of palladium catalyst and high safety requirements of catalytic hydrogenation equipment, and achieve the effect of short steps, low equipment requirements and high yield
CN112575044AActive Publication Date: 2021-03-30SHANDONG BOYUAN PHARM CO LTD
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
SHANDONG BOYUAN PHARM CO LTD
Publication Date
2021-03-30

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Abstract

The invention discloses a method for preparing a CDK4 / 6 inhibitor key intermediate through a chemical enzyme method. The method comprises the following steps: firstly, carrying out halogen / magnesium exchange on 5-bromo-2-nitropyridine and tert-butyl magnesium chloride to generate a Grignard reagent, and then carrying out addition reaction with N-tert-butyloxycarboryl-4-bromopiperidine to obtain 4-(6-nitropyridine-3-yl)piperidine-1-tert-butyl formate; and then creatively using nitroreductase (assisted by reductive coenzyme I) to reduce the 4-(6-nitropyridine-3-yl)piperidine-tert-butyl formate into 4-(6-aminopyridine-3-yl)piperidine-1-tert-butyl formate. The method has the advantages of short steps, simple operation, mild reaction conditions, high safety, no heavy metal catalyst, environmental protection, good product quality, high yield and low cost.
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Description

technical field

[0001] The invention relates to a method for preparing a CDK4 / 6 inhibitor key intermediate (4-(6-aminopyridin-3-yl)piperidine-1-carboxylate tert-butyl ester) by chemical-enzymatic method, which belongs to the technical field of organic synthesis. Background technique

[0002] Cyclin-dependent kinases CDKs are a class of protein kinases that play a role in cell cycle regulation and are important factors in cell cycle regulation, among which CDK4 / 6 is the human cell division and proliferation cycle (G1 phase S phase G2 phase M phase) These two kinases are hyperactive and exhibit significant activity in many malignancies. CDK4 / 6 inhibitors induce cell cycle arrest through the CDK4 / 6-Rb signaling pathway, thereby inhibiting cell proliferation and exerting anti-tumor effects. tert-butyl 4-(6-aminopyridin-3-yl)piperidine-1-carboxylate has attracted much attention as a key intermediate of CDK4 / 6 inhibitors.

[0003] 4-(6-aminopyridin-3-yl) piperidine-1-carboxylic ...

Claims

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