Preparation for medicinal intermediate 6-chloro-5-fluroindole for synthesizing anti-cancer medicament

Abstract

The invention relates to preparation for a medicinal intermediate 6-chloro-5-fluroindole for synthesizing an anti-cancer medicament, which comprises the following steps that: firstly, 3-fluro-4-aminotoluene reacts in a concentrated sulfuric acid system, the pH value is adjusted to be neutral after the reaction, and the mixture is filtered to obtain 3-fluro-4-amino-6-nitrotoluene; secondly, a sodium nitrite solution and cuprous chloride are added in the concentrated sulfuric acid system, and the mixture is diluted by clear water to obtain 3-fluro-4-chloro-6-nitrotoluene; thirdly, the 3-fluro-4-chloro-6-nitrotoluene and N, N-dimethyl formamide dimethylacetal react in a molecular sieve drying DMF system to obtain 2-(methylamino) ethylene-4-fluro-5-chloronitrobenzene; and finally, iron powder is added into an acetic acid system, and after the reaction, the mixture is recrystallized by using a mixed system containing petroleum ether to obtain the white 6-chloro-5-fluroindole. The method has the advantages of simple operation, environmental friendliness, high purity and low cost, and is suitable for industrialized production.

Description

technical field [0001] The invention belongs to the field of preparation of fluorine-containing indole as a pharmaceutical intermediate, and in particular relates to the preparation of a pharmaceutical intermediate 6-chloro-5-fluoroindole used for synthesizing anticancer drugs. Background technique [0002] At present, since 6-chloro-5-fluoroindole is an important intermediate for the preparation of new anti-cancer drugs, several major pharmaceutical companies have research and development projects for new anti-pancreatic cancer drugs, and many of them have entered the clinical stage. Therefore, the intermediate The overall demand is gradually exuberant, and it has great potential to earn foreign exchange through export. For example, the preparation of GlaxoSmithKline's new drug "GSK-3β inhibitor" uses this intermediate, and the final raw material drug can be obtained through a simple reaction, which can effectively simplify the drug production process. [0003] But now man...

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Problems solved by technology

[0003] But now many methods for preparing 6-chloro-5-fluoroindole are known, 1: (Tetrahedron Letters Volume 43, Issue 42, 14 October 2002, Pages 7581-7583) 2: (Bioorganic & Medicinal Chemistry Letters Volume 14, Issue 9, 3 May 2004, Pages 2367-2370) related synthesis methods are mentioned in the literature, but the synthesis process can only achieve a small amount of gram-level synthesis in the laboratory, the process is difficult to scale up, the post-treatment is complicated, the yield is not high, and the pollution Larger, little industrial value

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