Method for preparing pimavanserin crystal form C

A technology of Pimaserin and crystal form, which is applied in the field of preparation of Pimaserin Crystal Form C, can solve the problems that are not conducive to industrialization and restrict the application of Pimaserin Crystal Form C, and achieve industrialization and operation. Effects in simple steps

Active Publication Date: 2016-09-07
LIANGJIANG MEDICINE CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The above methods are not conducive to industrialization, which restricts the application of Pimaserin Form C

Method used

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  • Method for preparing pimavanserin crystal form C
  • Method for preparing pimavanserin crystal form C

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preparation example Construction

[0018] The invention provides a method for preparing Pimaserin crystal form C, comprising:

[0019] The tartaric acid of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropoxy)-phenylmethyl)urea The crystalline form A of the salt was refluxed in acetone for 3-6 hours to obtain the crystalline form C of pipemaserin.

[0020] The inventive method of the present invention can realize the transformation of the Pimaserin crystal form through simple heating and reflux, without deoxidizing the solvent, without inert gas protection, and without adding seed crystals. The operation steps are simple, no harsh conditions are required, and more conducive to industrialization.

[0021] In the present invention, N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropoxy)-phenylmethyl) Form A of urea tartrate was suspended in acetone and refluxed.

[0022] The N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropoxy)-phenylmethyl)urea The ratio of the m...

Embodiment 1

[0029] 3.0g of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropoxy)-phenylmethyl)urea The crystal form A of tartrate salt was heated and refluxed in 24mL of acetone solvent for 3 hours, and the temperature was slowly lowered to 20-30°C. After vacuum filtration, the filter cake was rinsed with a certain amount of acetone, and the white filter cake was dried at 40-50°C. 2.5 g of Form C are obtained. Yield 83.3%, purity 99.84%.

[0030] The melting point was determined to be in the range of 165-170°C, and DSC showed a melting point of 177°C. See attached for DSC-TGA diagram figure 1 . See attached for XRPD figure 2 , and the XRPD of Form C reported in the literature Figure 1 Sincerely. It can be seen that the method disclosed in the present application has prepared Pimaserin Form C.

Embodiment 2

[0032] 3.0g of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropoxy)-phenylmethyl)urea The crystal form A of tartrate salt was heated and refluxed in 30mL of acetone solvent for 6h, and the temperature was slowly lowered to 20-30°C. After vacuum filtration, the filter cake was rinsed with a certain amount of acetone, and the white filter cake was dried at 40-50°C. 2.4 g of Form C was obtained with a yield of 80.0% and a purity of 99.87%. The product was confirmed by XRPD detection.

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Abstract

The invention provides a method for preparing a pimavanserin crystal form C. The method comprises the step of: conducting reflux on a tartrate crystal A of N-(4-fluorobenzyl)-N-(1-methylpiperidine-4-yl)-N'-(4-(2-methyl propoxy)-phenyl methyl) urea in acetone for 3-6 h to obtain the pimavanserin crystal form C. The invention creatively realizes the crystal form transformation of pimavanserin by simple heating and refluxing, does not need deoxidation treatment of solvent, or the protection of inert gas, or addition of seeds; and the operation steps are simple without harsh conditions, and are more conducive to industrialization.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a preparation method of Pimaserin crystal form C. Background technique [0002] Pimaserin is useful in the treatment of conditions associated with serotonin receptors. Among them, crystal form C is the most effective. [0003] In the prior art, when preparing Pimaserin Form C, the organic solvent must be degassed and prepared in an inert gas (nitrogen or argon) environment, and the conditions are very harsh. Or add crystal form C as a seed crystal to suspend and balance polymorph A to prepare crystal form C. The above methods are not conducive to industrialization, and restrict the application of Pimaserin Form C. [0004] In addition, patent CN101778821A reports that DSC indicates that the melting point of anhydrous crystal form A is about 133-135°C, and crystal form C shows an endothermic signal at 177°C. Contents of the invention [0005] In view of this, the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D211/58
CPCC07B2200/13C07D211/58
Inventor 邓治荣黄鑫贺耘冯立春
Owner LIANGJIANG MEDICINE CO LTD
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