Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Method for preparing pimavanserin and tartrate thereof

A technology for pimaserin and hemi-tartrate, which is applied in the field of improved preparation of pimaserin and its tartrate, can solve the problem of 4-(2-methylpropoxy)benzene which endangers the health of production members, is unsuitable for storage, and Problems such as poor stability of methyl isocyanate

Inactive Publication Date: 2017-10-24
SUNSHINE LAKE PHARM CO LTD
View PDF8 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] In this method, phosgene is used to prepare 4-(2-methylpropoxy) phenylmethyl isocyanate. Phosgene is highly toxic, has a great impact on the environment, and endangers the health of production members, and the reaction process needs to ensure that no Water, supporting equipment is required, the obtained 4-(2-methylpropoxy)phenylmethyl isocyanate has poor stability and is not suitable for storage

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for preparing pimavanserin and tartrate thereof
  • Method for preparing pimavanserin and tartrate thereof
  • Method for preparing pimavanserin and tartrate thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] The preparation of embodiment 1 compound 2

[0055] Dissolve (4.7g, 47.5mmol) BTC in 190ml DCM, cool down to 0°C and stir for 30min. (24g, 108mmol) compound 1 and (21.8g, 216mmol) triethylamine were dissolved in 50ml DCM. At 0°C, slowly drop the mixed solution into the above-mentioned triphosgene-dichloromethane solution, stir for 30 minutes after the dropwise addition, warm up to room temperature (30°C), stir and react for 24 hours, and the remaining amount of compound 1 is controlled by HPLC ≤ 1.0% . After the reaction was completed, the pH was adjusted to 5-6, the liquid was separated, extracted with DCM, the organic phases were combined, and the solvent was evaporated under reduced pressure to obtain 27.63 g of compound 2 with a yield of 90% and a purity of 98.2%.

[0056] LCMS-ESI + Characterization: 285.1[M+H + ].

[0057] 1 HNMR characterization: (400MHz, CDCl 3 )7.28(t, J=8.0,2H),6.99(t,J=10.0,2H),5.19(d,J=12.0,1H),3.93(d,J=16.0,1H),3.58(m,3H ), 3.54(m,1...

Embodiment 2

[0059] The preparation of embodiment 2 compound 2

[0060] 14.7g of BTC (0.44eq, 47.50mmol) was dissolved in 190ml of dichloromethane (8vol), and the temperature was lowered to 0°C and stirred. 24g (107.96mmol) of compound 1 and 21.8g of triethylamine (2.0eq, 215.92mmol) were miscibly dissolved in 50ml of dichloromethane (2vol), and the mixed solution was slowly Add dropwise the above-mentioned triphosgene in dichloromethane solution. After the dropwise addition was completed and stirred for 30 min, the temperature was raised to room temperature (30° C.) for reaction. The reaction was stirred at room temperature for 24 hours, and the detection of compound 1 by HPLC was below 3%. After the reaction was completed, the pH was adjusted, the liquid was separated, extracted, and the organic phase was rotary evaporated in vacuum to obtain 27.63 g of liquid compound 2 with a yield of 90%.

Embodiment 3

[0061] The preparation of embodiment 3 compound 2

[0062] Dissolve 9.4g of BTC (0.44eq, 31.67mmol) in 130ml of dichloromethane (8vol), and stir at -5°C. Mix 16g of compound 1 (71.97mmol) and 11.36g of pyridine (2.0eq, 143.94mmol) in 30ml of DCM (2vol), and slowly drop the mixed solution into the above-mentioned Sanko gas in dichloromethane solution. After the dropwise addition was completed and stirred for 30 minutes, the temperature was raised to room temperature (30° C.) and the reaction was stirred for 18 hours. Compound 1 was detected to be below 1% by HPLC. After the reaction was completed, the pH was adjusted, the liquid was separated, extracted, and the organic phase was rotary evaporated in vacuum to obtain 19.04 g of liquid compound 2 with a yield of 92.9%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides an improved method for preparing pimavanserin and tartrate thereof. The method comprises the following steps: taking a compound 4-(4-fluorobenzylamino)-1-methylpiperidine as a starting material and carrying out acylation reaction on the starting material and triphosgene in the presence of triethylamine to prepare a compound (4-fluorobenzyl)-(1-methylpiperidine-4-yl)carbamyl chloride; then taking the (4-fluorobenzyl)-(1-methylpiperidine-4-yl)carbamyl chloride and 4-isobutoxybenzylamine to react in the presence of triethylamine, so as to prepare the pimavanserin and the tartrate thereof. The method provided by the invention is simple, efficient and economical and the quality of an intermediate is controllable, so that the method is suitable for industrial preparation.

Description

technical field [0001] The invention belongs to the technical field of organic and pharmaceutical synthesis, and in particular relates to an improved method for preparing pimaserin and tartrate thereof. Background technique [0002] Pimaserin (also known as Pimavanserin), generic name Pimavanserin, trade name Nuplazid, also known as N-[(4-fluorophenyl)methyl]-N-(1-methyl-4-piperidin Pyridyl)-N'-[[4-(2-methylpropoxy)phenyl]methyl]-urea, 1-(4-fluorobenzyl)-1-(1-methylpiperidine- 4-yl)-3-[4-(2-methylpropoxy)benzyl]urea or, N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl base)-N'-(4-(2-methylpropoxy)phenylmethyl)urea or ACP-103, the structural formula is as follows: [0003] [0004] Formula (I) Pimaserin is a non-dopamine neurotransmitter substance, and as an inverse agonist of 5-HT2A receptor, it can selectively block 5-HT2A receptor without affecting the effect of dopamine. Pimaserin exhibits antipsychotic, antikinesia and antiinsomnia activities. [0005] Formula (...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D211/58
CPCC07D211/58
Inventor 雷鑫田发银何方李东明
Owner SUNSHINE LAKE PHARM CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com