Preparation method of Rucaparib intermediate

An intermediate, indole technology, applied in the field of pharmaceutical synthesis, can solve the problems of low catalytic hydrogenation reaction yield, long reaction steps, unfavorable environmental protection and the like, and achieve the effects of shortening the preparation period, simplifying the route and improving the selectivity

Inactive Publication Date: 2017-05-31
伦俊杰
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] This route uses a large amount of nitric acid and sulfuric acid, which is not conducive to environmental protection. The reaction step temperature of DMFDMA is high, and the hea

Method used

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  • Preparation method of Rucaparib intermediate
  • Preparation method of Rucaparib intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1 Preparation of 3-fluoro-5-methoxyacylbenzenediazotetrafluoroborate

[0036] Add 1.69g (10mmol) of methyl 3-amino-5fluorobenzoate to 10ml of 30% boron tetrafluoride solution, cool down to -5°C, and slowly add 4mol / L NaNO 2 2.9mL of the solution of 3-fluoro-5-methoxyacylbenzenediazotetrafluoroborate was obtained by keeping the temperature at -5—0°C during the dropwise addition for 30 minutes. %.

Embodiment 2

[0037] Example 2 Preparation of 3-fluoro-5-methoxyacylbenzenediazotetrafluoroborate

[0038] Add 1.69g (10mmol) of methyl 3-amino-5fluorobenzoate to 10ml of 30% boron tetrafluoride solution, cool down to -10°C, and slowly add 5mol / L NaNO 22.3mL of the solution of 3-fluoro-5-methoxyacylbenzenediazotetrafluoroborate was obtained by keeping the temperature at -5—0℃ during the dropwise addition for 30 minutes. %.

Embodiment 3

[0039] Example 3 Preparation of 3-fluoro-5-methoxyacylbenzenediazotetrafluoroborate

[0040] Add 1.69g (10mmol) of methyl 3-amino-5fluorobenzoate to 10ml of 40% boron tetrafluoride solution, cool down to -5°C, and slowly add 4mol / L NaNO 2 3.0mL of the solution, the temperature was kept at -5—0°C during the dropwise addition, reacted for 30 minutes, filtered, washed with methanol, and 2.47g of 3-fluoro-5-methoxyacylbenzenediazotetrafluoroborate was obtained, with a yield of 92.2 %.

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Abstract

The invention belongs to the field of medicine synthesis, and in particular relates to a preparation method of a Rucaparib intermediate 6-fluoro-3-[(E)-2-nitroethylene]-1H-indole-4-methyl formate. 3-amino-5-methyl fluorobenzoate is used as a raw material in the method, which reacts with a zinc reagent of 2-(2-bromoethyl)-1,3-dioxolane after being diazotized, then is hydrolyzed, and reacts with nitromethane. The preparation method has cheap and easily available materials, a refined reaction route, high reaction selectivity and high yield.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a preparation method of Rucaparib intermediate 6-fluoro-3-[(E)-2-nitrovinyl]-1H-indole-4-carboxylic acid methyl ester. Background technique [0002] Rucaparib (AG014699) chemical name: 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-3,4,5,6-tetrahydro-6H-benzazepine[5, 4,3-cd]indol-6-one phosphate, molecular formula: C 19 h 18 FN 3 O·H 3 PO 4 , CAS number: 459868-92-9, its structural formula is as follows. [0003] [0004] Rucaparib is an antineoplastic drug developed by Pfizer. It inhibits the activity of polyadenosine diphosphate-ribose polymerase (PARP), thereby enhancing the effect of radiotherapy and DNA-damaging chemotherapy drugs. A large number of clinical experiments have proved that it has low toxicity and side effects, clear effect and good tolerance, and can be used for the potential treatment of cancer, including solid tumors such as breast cancer and o...

Claims

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Application Information

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IPC IPC(8): C07D209/10
CPCC07D209/10
Inventor 陈令浩
Owner 伦俊杰
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