Preparation method of Rucaparib intermediate

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...

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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 heat is violently released during the reaction. At the same time, the reaction yield of catalytic hydrogenation is low, the reaction steps are long, and the total yield is only about 15%.

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