Method for preparing green innovative side chain for biapenem

Abstract

The invention provides a method for preparing a green innovative side chain for biapenem. The method comprises the following steps of: reacting a compound and a compound NH2NH2.H2O under the action of a compound EtOH to obtain a compound HCONHNHCHO(I); under an action of a compound K2CO3 and a compound, reacting the HCONHNHCHO(I) to obtain a compound (II); reacting the compound (II) with compounds KBr and H2O2 in the presence of a catalyst to form a compound (III); and reacting the compound (III) the a compound K2CO3 reacted to obtain a final compound.

Description

technical field The invention relates to the field of synthesis of pharmaceutical intermediates, in particular to a preparation method of a green innovative biapenem side chain intermediate. Background technique Transformation of the research field of lactam antibiotics. In the research on such as penems, carbapenems, oxycephem, and carbacephem, some good varieties have emerged, which has increased the interest of researchers in this field. Or there are as many as a dozen varieties of pre-clinical research. Especially carbapenem antibiotics, which have been used clinically include imipenem (IPM), meropenem (meropenem), panipenem (panipenem) and baipenem, etc. Excellent curative effect for various bacterial infections, less toxic and side effects. Biapenem has strong antibacterial activity against Gram-positive bacteria, Gram-negative bacteria (including drug-resistant Pseudomonas aeruginosa), anaerobic bacteria, etc.; it is stable to β-lactamase; it is stable to DHP-1 S...

AI Technical Summary

Problems solved by technology

Route 1 needs 9 steps of reaction, but its raw material 1,2-bis(tert-butyloxycarbonyl)hydrazine also needs to be synthesized, and not only the yield is low, but also the reaction conditions are harsh, the operation is complicated, most of the reagents are imported, the price is expensive, and it is very expensive. Difficult to carry out industrial production

Route 2 requires 11 steps of reaction, but its raw materials are easy to get, the required conditions are relatively simple, most of the reagents are domestically produced, and the price is cheap, but the yield is low, and the highest yield is 18%; wherein 4-bromo-1,2- The yield of diformylpyrazolidine (the formula IV compound in the present invention) is only about 36% [Shi Hepeng, Chinese Journal of Medicinal Chemistry, 2005, 15 (1): 45-47], the middle side of Chinese patent application CN101121716A The total yield of chain 6,7-dihydro-6-mercapto-5H-pyrazolo[1,2-a][1,2,4]triazole chloride was about 5%, of which 4-bromo- The yield of 1,2-diformylpyrazolidine is only about 30%, and more toxic reagents are used in the prior art, which seriously pollutes the environment

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