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

A kind of preparation method of rucaparib key intermediate

An intermediate and key technology, applied in the field of drug synthesis, can solve the problems of low yield of catalytic hydrogenation reaction, unfavorable industrial production, severe heat release, etc., and achieve easy and effective control of reaction conditions, reasonable route design, and cheap and easy-to-obtain raw materials Effect

Active Publication Date: 2020-08-14
安庆奇创药业有限公司
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In this indole cyclization route, the temperature of the reaction step of DMFDMA is relatively high, and the reaction is violently exothermic, and the reaction yield of catalytic hydrogenation is low at the same time, which is not conducive to industrial production

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
  • A kind of preparation method of rucaparib key intermediate
  • A kind of preparation method of rucaparib key intermediate
  • A kind of preparation method of rucaparib key intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] (1) Synthesis of 6-fluoro-3-formyl-1H-indole-4-carboxylic acid methyl ester (compound B):

[0027] Add 3-fluoro-5-hydrazino-benzoic acid methyl ester (9.20g, 0.05mol) and malondialdehyde (6.49g, 0.09mol) into 50mL water, add 90% formic acid (1.15g, 0.025mol), then add Sodium hydrogen phosphate (21.30g, 0.15mol), the reaction mixture was reacted at 40°C for 5 hours, TLC was spotted to confirm the completion of the reaction, water (200mL) and ethyl acetate (200mL x 3) were added for separation and extraction, and the organic layer was separated and collected , the organic layer was washed with saturated aqueous sodium chloride solution (100 mL), and the organic phase was collected and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 9.36g white solid 6-fluoro-3-formyl-1H-indole-4-carboxylic acid methyl ester (compound B), the yield was 84.6%, and the purity was 98.3% (HPLC area normalization method ) The reaction formula...

Embodiment 2

[0032] The preparation method is the same as in Example 1, but the molar ratio between compound A, malondialdehyde, catalyst and buffering agent in step (1) is 1.0: 1.5: 0.1: 2.0, the reaction temperature is 80 ° C, and the reaction time is 2 hours 8.27g of methyl 6-fluoro-3-formyl-1H-indole-4-carboxylate (compound B) was obtained as a white solid, with a yield of 74.8% and a purity of 94.4% (HPLC area normalization method).

Embodiment 3

[0034] The preparation method is the same as in Example 1, but the molar ratio between compound A, malondialdehyde, catalyst and buffering agent in step (1) is 1.0: 2.5: 0.6: 4.0, the reaction temperature is 20 ° C, and the reaction time is 8 hours 7.28g of methyl 6-fluoro-3-formyl-1H-indole-4-carboxylate (compound B) was obtained as a white solid, with a yield of 65.8% and a purity of 93.5% (HPLC area normalization method).

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 a Rucaparib key intermediate. The method includes the steps of: (1) subjecting a compound A and malondialdehyde to Fischer indole synthesis reaction toobtain a compound B; and (2) reacting the compound B with nitromethane to obtain a target product 6-fluoro-3-[(E)-2-nitrovinyl]-1H-indole-4-methyl formate, i.e. the Rucaparib key intermediate. Compared with the prior art, the preparation method of the Rucaparib key intermediate provided by the invention has the advantages of reasonable route design, cheap and easily available raw materials, greenand environmental protection, and easily and effectively controllable reaction conditions.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a preparation method of a key intermediate of Rucaparib. Background technique [0002] The trade name of Rucaparib is Rubraca (alias AG-014699, AG-14699, PF-01367338, PF-1367338), and its chemical name is 8-fluoro-2-{4-[(methylamino)methyl)]phenyl}-1 , 3,4,5-tetrahydro-6H-azepine[5,4,3-cd]indole-6-copper phosphate, the molecular formula is C 19 h 18 FN 3 O·H 3 PO 4 , the molecular weight is 418.34, and its chemical structural formula is: [0003] [0004] Ovarian cancer ranks sixth in the incidence of female malignancies. Although the incidence of ovarian cancer is not as high as that of breast cancer, its mortality rate ranks first among gynecological malignancies. Rucaparib is a polyadenosine diphosphate-ribose polymerase (PARP) inhibitor. Its original research company is Newcastle University, and its research company is Clovis Oncology. Rucaparib is the fir...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/10
CPCC07D209/10
Inventor 吴学平储贻结时珠勇
Owner 安庆奇创药业有限公司
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