A kind of preparation method of chlorpromazine hydrochloride

Abstract

The invention relates to a preparation method of chlorpromazine hydrochloride, which belongs to the technical field of medicine preparation. The present invention takes 2-chlorophenothiazine and N, N-dimethyl-3-chloropropylamine as raw materials, adopts N-methylpyrrolidone organic solvent, reacts under the effect of 4-dimethylaminopyridine catalyst, and generates chlorine Promethazine, the gained chlorpromazine and hydrogen chloride gas form a salt, namely get chlorpromazine hydrochloride. The present invention does not need to use toluene toxic reagent, and adopts N-methylpyrrolidone organic solvent, which is not only more environmentally friendly, but also more conducive to the recovery of chlorpromazine, and improves the yield and purity of chlorpromazine. And without adding a large amount of sodium hydroxide, by selecting 4-dimethylaminopyridine, it can replace sodium hydroxide and tetrabutylammonium bromide in the original process, and significantly improve the yield and purity of chlorpromazine hydrochloride. Controlling the conditions of the hydrochloric acid salt-forming reaction is more favorable for the crystallization and purification of chlorpromazine hydrochloride, and higher purity chlorpromazine hydrochloride can be obtained.

Description

technical field [0001] The invention relates to a preparation method of chlorpromazine hydrochloride, which belongs to the technical field of medicine preparation. Background technique [0002] Chlorpromazine hydrochloride is a representative drug in phenothiazine drugs. For the central nervous system, a small dose has a stabilizing effect, and a large dose of continuous use has an antipsychotic effect. This product inhibits the subthalamic body temperature regulation center, making the body temperature rise and fall with the ambient temperature, and cooperates with other drugs to make the body temperature drop below normal body temperature. Metabolism Reduced, called artificial hibernation. It is mainly used for antipsychotics, strengthening hypnotics, anesthetics, analgesics and anticonvulsants. [0003] At present, the commonly used preparation method of chlorpromazine hydrochloride is to use 2-chlorophenothiazine of the main ring and N, N-dimethyl-3-chloropropylamine a...

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Problems solved by technology

[0003] At present, the commonly used preparation method of chlorpromazine hydrochloride is to use 2-chlorophenothiazine of the main ring and N, N-dimethyl-3-chloropropylamine as raw materials, and react with sodium hydroxide as a condensation agent to generate chlorpromazine , the gained chlorpromazine and hydrogen chloride gas form a salt, promptly get chlorpromazine hydrochloride, but the yield of this preparation method gained chlorpromazine hydrochloride is not very high, and the molar yield of condensation reaction is about 70%, and quality difference is big

Wherein, in CN201210068205.4 a kind of synthetic technique of chlorpromazine hydrochloride, with main ring 2-chlorophenothiazine and side chain N, N-dimethyl-3-chloropropylamine as raw material, with sodium hydroxide, Tetrabutylammonium bromide generates chlorpromazine for condensation agent reaction; Gained chlorpromazine and hydrogen chloride gas salify, obtain chlorpromazine hydrochloride, it provides a kind of preparation method of the higher chlorpromazine hydrochloride of productive rate, By selecting sodium hydroxide and tetrabutylammonium bromide as the condensation agent, strictly controlling the ratio of raw materials and the indicator end point of the salt-forming reaction, the molar yield of chlorpromazine can reach more than 90%, the reaction process is complicated, and the Reagent research is strict, and toxic reagents such as toluene and a large number of alkali catalysts are used in it. In industrial use, not only the production efficiency is low, it does not conform to the concept of green environmental protection, but there are many uncontrollable factors that affect the yield of chlorpromazine hydrochloride and purity, and the yield and purity of target product chlorpromazine hydrochloride are not involved in this prior art

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