Preparation method of pimavanserin hemitartrate crystal form C

Abstract

The invention discloses a preparation method of a pimavanserin hemitartrate crystal form C. The method includes the steps of: (1) under the protection of an inert gas, adding pimavanserin free alkali into butanone, and conducting dissolving, then adding tartaric acid to carry out reaction to obtain a reaction solution; (2) carrying out crystallization, filtering and drying on the reaction solution obtained in step (1), thus obtaining the pimavanserin hemitartrate crystal form C. The method adopts pimavanserin free alkali as the raw material, and successfully prepares the pimavanserin hemitartrate crystal form C. Compared with the prior art, the method provided by the invention is simple, safe and environment-friendly, shortens the stirring crystallization time from 3 days to 2-3 hours, greatly improves the production efficiency, has good economic benefits, and is very suitable for industrial production.

Description

Technical field [0001] The invention relates to a method for preparing the crystal form C of pimaserin hemitartrate. Background technique [0002] Pimaserin hemi-tartrate, the chemical name is N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropoxy) 基)phenylmethyl)urea tartrate (2:1), the English name is urea,N-[(4-fluorophenyl)methyl]-N-(1-methyl-4-piperidinyl)-N′-[[4 -(2-methylpropoxy)phenyl]methyl]-,(2R,3R)-2,3-dihydroxybutanedioate(2:1), is a serotonin 2A receptor inverse agonist, mainly used to treat hallucinations or For patients with Parkinson's disease such as delusions, the structural formula is as follows: [0003] [0004] Chinese patent CN 102153505 A reports a crystalline form C of pimaserin hemitartrate, which has good stability and water solubility. Its preparation methods are divided into two types: [0005] (1) Need for seed crystals: In the process of forming crystal form C of pimaserin hemi-tartrate, crystal form C needs to be added as seed crystals....

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Problems solved by technology

[0005] (1) Seed crystals are required: in the process of forming Form C of pimaserin hemitartrate, Form C needs to be added as a seed crystal, as in Examples 33-36, 38-46, and 54. The disadvantages are : In the case that there is no crystal form C or the crystal form C cannot be obtained, the method cannot be implemented at all;

[0006] (2) No need for seed crystals: 25g of pipemaserin hemitartrate was suspended in 100ml of THF, and the suspension was stirred at 30°C for 3 days, the solid was filtered off and dried under reduced pressure at 40°C for 2 hours to obtain Crystal form C, its disadvantages are: the stirring and crystallization time is as long as 3 days, the production efficiency is very low, the economic benefit is poor, and it is not suitable for industrial production

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