Preparation method of Niraparib

A reagent and solvent technology, applied in the field of preparation of niraparib, can solve the problems of long synthetic route and high cost

Inactive Publication Date: 2017-05-31
NANJING CORE TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] Route 3 Org.Process Res.Dev.2014,18,215-227 reports: (S)-3-(4-aminophenyl)piperidine is derived from (S)-3-(4-aminophenyl)-2piperidine The reduction of ketones is obtained, while (S)-3-(4-aminophenyl)-2-piperidone is prepared by using specific enzymes through biological fermentation. This method has certain limitations, and the selected enzymes require specific Cultivated, and the synthetic route is longer and the cost is higher

Method used

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  • Preparation method of Niraparib
  • Preparation method of Niraparib
  • Preparation method of Niraparib

Examples

Experimental program
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Effect test

example 1

[0044] Example 1 Add 120 mL of benzyl bromide to 30.0 g (0.15 mol) of compound 2, heat the reaction solution to 110 ° C for 10 hours, then cool to room temperature, a solid is precipitated, the solid is filtered out, and washed twice with hexane, and the The obtained solid was dried in a blast oven at 45° C. to obtain 45.2 g of brown color.

[0045]

example 2

[0046] Example 2 Compound 4 was prepared with reference to Example 1

[0047]

example 3

[0048] Example 3 Add compound 3 (43.0g, 0.12mol) to 130mL of methanol, cool the reaction solution to 3-5°C, add sodium borohydride (18.2g, 0.48mol) in partitions, and stir at this temperature after the addition is complete After 30 minutes, rise to room temperature and react for 8 hours. After distilling off most of the methanol under reduced pressure, add 110 mL of water and extract with ethyl acetate twice (2*150 mL), and dry the organic phase with anhydrous sodium sulfate. , the organic phase was steamed under pressure to obtain 22.8 g of light yellow solid.

[0049]

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Abstract

The invention discloses a preparation method of a compound 2-[4-((3S)-3-piperidin) phenyl]-2H-indazole-7-carboxamide; through the reaction of 4-nitryl phenylpyridine and benzyl halides, the benzyl quaternary ammonium salt is generated; the pyridine quaternary ammonium salt is restored selectively through sodium borohydride; under the effect of palladium reagent, the 3-(4- aminophenyl)- piperidine is obtained the (S)-3-(4- halogenated phenyl) piperidine is obtained through manually splitting the reagent, and then condensed with 3- formyl group-2- nitrobenzene methyl benzoate and forms pyrazol ring under the effect of sodium azide; through aminolysis, the Niraparib (molecule entity is: 2-[4-((3S)-3-piperidin) phenyl]-2H-indazole-7-carboxamide) is prepared.

Description

[0001] Technical field: the present invention belongs to the field of chemical medicine, specifically a method for preparing 2-[4-((3S)-3-piperidinyl)phenyl]-2H-indazole-7-carboxamide [0002] Background technique: [0003] Niraparib (molecular entity is 2-[4-((3S)-3-piperidinyl)phenyl]-2H-indazole-7-carboxamide), belongs to PARP inhibitor, which is a class of PARP gene target It is not effective for any cancer, but it is mainly used for patients with BRCA1 / 2 gene mutations, which embodies what is often called "precision medicine" for cancer. [0004] The full name of PARP is poly(ADP-ribose) polymerase, which can recognize DNA single-strand breakpoints and initiate DNA repair. Since many chemotherapy drugs induce DNA damage, and cancer cells develop drug resistance through DNA repair, PARP inhibitors were developed in the 1990s in an attempt to enhance the efficacy of chemotherapy drugs. The bumpy journey of PARP inhibitors began here. The initial research was not smooth. The...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/10
CPCC07D401/10C07B2200/07
Inventor 王雪根何凌云余洋魏超
Owner NANJING CORE TECH CO LTD
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