Preparation method of olaparib drug intermediate

Abstract

The invention provides a preparation method of an olaparib drug intermediate, and particularly relates to the technical field of preparation of drug intermediates. The method comprises the steps thatS1, 2-carboxybenzaldehyde, triethylamine and dichloromethane are mixed and stirred, then dimethyl phosphite is added for a reaction at the room temperature, methane sulfonic acid is added, a reactionsolution is concentrated to dryness, water is added for beating, filtering and drying are conducted, and beating with petroleum ether is conducted to obtain a white solid; S2, the solid obtained in the first step, 3-cyano-4-fluorobenzaldehyde and dichloromethane are mixed and then cooled, triethylamine is added dropwise for a reaction, a reaction solution is concentrated to dryness, water is addedfor beating, filtering and drying are conducted, and beating with methyl tert-butyl ether is conducted to obtain a white solid; S3, the solid obtained in the second step is mixed with water, coolingis conducted, hydrazine hydrate is added for a reaction, then acetone is added, a NaOH aqueous solution is added for a reaction, cooling is conducted to the room temperature, extraction is conducted,the pH value is adjusted, the white solid is precipitated, and filtering, rinsing with cold water and recrystallization are conducted to obtain the white solid. The preparation method has the advantages that the yield is increased, the production cost is reduced, and the operation is simple and convenient.

Description

technical field [0001] The invention belongs to the technical field of preparation of pharmaceutical intermediates, in particular to a preparation method of olaparib pharmaceutical intermediates. Background technique [0002] Olaparib (Olaparib), produced by AstraZeneca, is the first oral ADP-ribose polymerase (PARP) inhibitor currently on the market. PRAP enzymes are key enzymes required for healthy cells to repair themselves. However, , cancer cells also use PRAP to repair DNA damage, thereby promoting cancer cell growth and increasing the mortality rate of patients. The drug olaparib can selectively bind and inhibit the function of PRAP, thereby inhibiting the repair of DNA damage in cancer cells, especially cancer cells lacking the function of BRCA1 or BRCA2 (genes encoding tumor suppressor factors), which can Effectively controls tumor progression and promotes its shrinkage. Olaparib is mainly researched and applied in the treatment of ovarian cancer, breast cancer, p...

AI Technical Summary

Problems solved by technology

[0005] In order to solve the lower problem of yield and productive rate of existing 2-fluoro-5-[(4-oxo-3H-2,3-naphthyridine) methyl] benzoic acid, the object of the invention is A preparation method of an olaparib drug intermediate is provided, which has the advantages of increasing yield, reducing production cost, and being easy to operate