Supercharge Your Innovation With Domain-Expert AI Agents!

Preparation method of intermediate of lurasidone

A technology for lurasidone and intermediates, which is applied in the field of pharmaceutical synthesis, can solve the problems of harsh reaction conditions in the synthesis process, potential safety hazards, high temperature and high pressure, etc., and achieves the effects of less impurities, simple preparation process and high yield

Inactive Publication Date: 2014-07-02
上海信凯生物医药科技有限公司
View PDF0 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The technical problem solved by the present invention is to provide a preparation method of a lurasidone intermediate in order to overcome the harsh reaction conditions of the existing synthesis process, the need for high temperature and high pressure, and the existence of potential safety hazards.

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
  • Preparation method of intermediate of lurasidone
  • Preparation method of intermediate of lurasidone
  • Preparation method of intermediate of lurasidone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Synthesis of cis-5-norbornene-exo-2,3-dicarboximide (Compound 4)

[0033] Add 30ml of xylene, 20g of the compound cis-5-norbornene-exo-2,3-dicarboxylic anhydride, 14.6g of urea into a 250ml three-necked flask, heat to 135°C and stir for 6 hours, then cool down and distill off the solvent under reduced pressure. Recrystallize with 120ml of water, filter, and dry the filter cake at 70°C to obtain 17.2g of compound 4, yield: 86%, melting point: 160-162°C, 1H-NMR (CD 3 OD)δ: 1.38(m, 1H), 1.51(m, 1H), 2.71(d, J=1.6Hz, 2H), 3.16(m, 2H), 6.29(m, 2H), HPLC purity: 99.1%, Endo isomer product 0.3%, percentage is mass fraction.

Embodiment 2

[0035] Synthesis of cis-5-norbornene-exo-2,3-dicarboximide (Compound 4)

[0036] Add 30ml of N,N-dimethylformamide, 20g of the compound cis-5-norbornene-exo-2,3-dicarboxylic acid anhydride, and 15.3g of ammonium formate into a 250ml three-necked flask, heat to 140°C and stir for 7 hours , cooled and evaporated the solvent under reduced pressure, recrystallized with 120ml of water, filtered, and dried the filter cake at 70°C to obtain 16.6g of compound 4, yield: 83%, endo isomer product 0.25%, percentages are mass fractions.

Embodiment 3

[0038] Synthesis of cis-5-norbornene-exo-2,3-dicarboximide (Compound 4)

[0039] Add 30ml of N,N-dimethylformamide, 20g of compound cis-5-norbornene-exo-2,3-dicarboxylic acid anhydride, 14.6g of urea into a 250ml three-necked flask, heat to 135°C and stir for 6 hours, The solvent was evaporated under reduced pressure, recrystallized with 120ml of water, filtered, and the filter cake was dried at 70°C to obtain 17.4g of compound 4, yield: 87%, endo isomer product 0.28%, percentages are mass fractions.

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 discloses a preparation method of an intermediate of lurasidone. The preparation method of an intermediate 3 of lurasidone comprises the following steps: (1) subjecting a compound represented by the formula 5 to carry out ammonolysis reactions with one or more components selected from urea, ammonium chloride, and organic acid ammonium in an organic solvent so as to obtain a compound 4; (2) subjecting the compound 4 obtained in the step (1) to carry out reactions with H2 in the presence of a palladium-carbon catalyst so as to obtain the intermediate 3 of lurasidone. The preparation method of an intermediate 4 of lurasidone comprising the following steps: in an organic solvent, subjecting one or more components selected from urea, ammonium chloride, and organic acid ammonium to carry out ammonolysis reactions with a compound represented by the formula 5 so as to obtain the intermediate 4 of lurasidone. The preparation method does not need high temperature or high pressure, and has the advantages of simple preparation technology, high yield, and suitability for amplification production.

Description

technical field [0001] The invention relates to the field of pharmaceutical synthesis, in particular to a preparation method of a lurasidone intermediate. Background technique [0002] Lurasidone (lurasidone) is a new type of atypical antipsychotic drug, which was approved by the US Food and Drug Administration (FDA) on October 28, 2010. Its trade name is Latuda and it is used for the treatment of schizophrenia. The following is a synthetic Lurasidone route: [0003] [0004] Compound 3 ((3AR,4S,7R,7AS)4,7-methylene-1H-isoindole-1,3(2H)-dione) is one of the main intermediates of lurasidone. It has been reported that its synthetic route is as follows: [0005] [0006] This synthesis process has the following disadvantages. The reaction temperature in the second step is as high as 190 ° C, and a high-pressure reactor is required. The reaction conditions are relatively harsh, and the configuration of the starting materials is prone to inversion at high temperatures (ab...

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): C07D209/56
CPCC07D209/94
Inventor 旷建良乔俊杰王征魏海洋薛峰刘厚权
Owner 上海信凯生物医药科技有限公司
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com