Preparation method of asenapine intermediate

Abstract

The invention discloses a novel preparation method of an asenapine intermediate, comprising the following steps of: carrying out cyclization in protonic acid including trifloromethanesulfonic acid by taking 3-(2-(4- chlorophenoxyl)-phenyl-4-hydroxyl-1-methyl-1H-pyrrole-2(5H)-ketone (compound 1) or 3-(5-chlorine-2-phenoxyl phenyl)-1-methyl-1H-pyrrole-2(4H)-ketone (compound 4) as a raw material to generate key intermediate compounds 2 and 4 of asenapine; and carrying out reduction reaction to obtain asenapine. The invention has the advantages of novel process route, high reaction yield and low production cost, and has greater application value and social economic effect.

Description

technical field The invention relates to a chemical synthesis method, in particular to a novel preparation method of an intermediate of Asenapine which can be used as a schizophrenic, and belongs to the field of organic synthesis. technical background The trade name of Asenapine is Saphris, developed by Organon BioSciences and produced by ScheringPlough. On August 14, 2009, the FDA approved the drug for the emergency treatment of adults with schizophrenia, mania, or mixed episodes with type I bipolar disorder. English chemical name of asenapine: (3aR, 12bR)-rel-5-chloro-2, 3, 3a, 12b-tetrahydro-2-methyl-1H-dibenz[2,3:6,7]oxepino[4 ,5-c]pyrrole; Chinese chemical name: trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxa Zhuo[4,5-c]pyrrole; molecular formula: C17H16ClNO; relative molecular mass: 285.77; CAS registration number: 65576-45-6. Preparation. WO2006106136, WO2007046554, US20090209608, and WO2008078482 reported that starting materials 1 and 5 were...

AI Technical Summary

Problems solved by technology

When the final product asenapine (compound 7) is synthesized by the above-mentioned route, there are problems that the reaction yield of compound 2 or 5 is low, impurities are difficult to remove, and there is a lot of waste water

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