Improved process of preparing Raltitrexed

Abstract

The improvement in the process of preparing Raltitrexed as antitumor medicine includes the reaction between N-(5-aminothienyl-2-formoxyl)-L-diethyl glutarate and methyl iodide at temperature raised to 100 deg.c in lucifugous condition with yield raised to 91 %; the replacement of sodium sulfide for iron powder as reductant to facilitate post-treatment and raise yield; the replacement of re-crystallization in mixed solvent of methanol and ether for column separation to expand the production capacity; and oxidizing 5-nitrothienyl-2-formaldehyde with chromic acid, rather than bromine, to eliminate toxicity and raise safety. The improved preparation process of Raltitrexed has high yield, great production capacity, low solvent consumption and high safety.

Description

technical field

[0001] The invention belongs to the technical field of medicine, and relates to an improvement of a process method of an antineoplastic drug raltitrexed. Background technique

[0002] Raltitrexed is an antineoplastic drug for the treatment of advanced colon cancer, head and neck tumors, and hormone-resistant prostate cancer. It is the first new first-line cytotoxic agent for the treatment of colorectal cancer registered in the UK in 30 years. There has been no new drug in the field of colon cancer treatment for 40 years, and its effect in the treatment of colon and rectal cancer has been hailed as a major advancement in the past 35 years. Raltitrexed is a quinazoline folate analog whose anticancer effects are produced through the specific inhibition of thymidine synthase. Its characteristics: (1) curative effect is similar to that of fluorouracil; (2) less toxic and side effects; (3) can replace fluorouracil.

[0003]

[0004] Raltitrexed preparation pat...

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