Prepn of Nim-tribenzyl histidine

Abstract

The present invention is the preparation process of Nim-tribenzyl histidine in medicine chemical technology field. The preparation process includes dropping or solution of dichloro dimethyl silane into mixture of histidine and organic solvent, dropping triethylamine to neutralize HCl produced in the forgoing step, reflux reaction and lowering temperature, adding organic solution of trityl chloride while dropping triethylamine to neutralize HCl produced, stirring to react to obtain protected silane compound, adding diluent ethyl acetate, adding water to eliminate protection to obtain coarse Nim-tribenzyl histidine product containing silane with less polarity and triphenyl methanol as impurity, extracting with ethyl acetate to eliminate impurity, washing with deionized water before recrystallization, collecting solid and drying to obtain Nim-tribenzyl histidine product. The process may be used in large-scale production with medium yield of 60-65%.

Description

technical field [0001] The present invention relates to a kind of N im - A process for the preparation of tritylhistidine. It belongs to the technical field of medicine and chemical industry. Background technique [0002] Existing preparation N im - Tritylhistidine has the following methods: [0003] 1) Use triphenylchloromethane (Trt-Cl) or triphenylmethanol (Trt-OH) to simultaneously introduce a trityl group on the α-amino group of histidine (His) and the imidazole ring nitrogen to obtain N-triphenyl Methyl-N im -trityl-histidine (Trt-His(Trt)), and then remove the trityl group on the α-amino group to make N im - Tritylhistidine (G.C. Stelakatos, et al., J. Amer. Chem. Soc. 1959, 81, 2884). This method involves the problem of regioselective deprotection. It is difficult to control the conditions of regioselective detrityl, and the product purity is difficult to meet the requirements, and the amount of triphenylchloromethane or triphenylmethanol is twice the theoretic...

AI Technical Summary

Problems solved by technology

Although this method is easy to operate and consumes less raw materials, it needs to use a large amount of halogenated hydrocarbons (especially chloroform) as a solvent, and methanol with high toxicity as a deprotectant, which causes great environmental pollution and is not conducive to large-scale production.