Preparation methods of 10 H-dibenzo[b,f][1,4]thiazepin-11-one and quetiapine

Abstract

The invention provides a method for synthesizing a quetiapine mother-ring intermediate, and the method comprises the following steps: esterification of 2-nitro - 2'-carboxyl diphenyl sulfide, and under the right conditions, nitroreduction simultaneously with ester aminolysis to obtain the product 10 H-dibenzo[b,f][1,4]thiazepin-11-one and quetiapine by a one pot method. Compared with a traditional method, the method has the advantages of being simple in operation, high in yield, more suitable for industrial production, and the like.

Description

technical field [0001] The present invention relates to the technical field of medicine and organic synthesis, in particular to the preparation method of the compound of formula (I), whose chemical name is 10H-dibenzo[b,f][1,4]thiazepine-11-one, the compound Is an intermediate for the preparation of quetiapine. Background technique [0002] Quetiapine hemifumarate (quetiapine hemifumarate, 1, trade name Seroquel), chemical name 11-[4-[2-(2-hydroxyethoxy)ethyl]-1-piperazinyl]diphenyl And [b, f] [1, 4] thiazepine hemifumarate, the first-line atypical phenothiazine antipsychotic drug developed by British AstraZeneca and approved by the FDA in 1997, It can block multiple neurotransmitter receptors such as dopamine (DA) and 5-hydroxytryptamine (5-HT) in the brain, and has a broad-spectrum curative effect on various symptoms of schizophrenia, so the development of this drug has broad market prospects. [0003] The synthesis method of 10H-dibenzo[b,f][1,4]thiazepin-11-one is summ...

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Problems solved by technology

[0003]10H-dibenzo[b,f][1,4]thiazepine-11-one synthesis method is summarized. The previous literature mainly includes the following three items: The first route is to generate 2-phenylthiophenylcarbamate through the reaction of 2-aminodiphenylsulfide and phenylchloroformate, and synthesize 10H-dibenzo[b,f through intramolecular ring closure of polyphosphoric acid. ][1,4]thiazepin-11-one (EP282236), the yield of this route is relatively high, but the phenol with large environmental pollution is generated in the reaction process, which is not suitable for industrial production; route two, 2-aminodiphenyl Thioethers and triphosgene generate isocyanates, and then cyclize under the effect of PPA. The yield of this method is improved, but the very toxic triphosgene is introduced in the reaction, which is greatly restricted in industrial production (Chinese pharmaceutical industry Journal, 2004, 35(12):705-707.); route three, the literature selects the reaction of o-halogenated nitrobenzene and thiosalicylic acid, and the resulting product is reduced with FeSO4, and further used Mother ring produced by dehydration and cyclization of concentrated sulfuric acid

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