A kind of 4-substituted amino-6-methoxycarbonylbenzofuro[2,3-d]pyrimidine compound and its preparation and application

Abstract

The invention discloses a 4-substituted mino-6-methoxycarbonyl group benzofuran and [2,3-d] pyrimidine compound and a preparing method thereof. 2-amino-3-cyano benzofuran-5-carboxylic acid methyl ester and ortho-formate are dissolved into a solvent A, a reaction is conducted under the acid catalysis and heating conditions, and concentration is carried out after the reaction is finished to obtain an intermediate; then, the intermediate and an amine compound are subjected to a reflux reaction in a solvent B, a reaction product is subjected to separation and purification treatment, and a product is obtained. The compound has potential biological activity, important research value and good application prospects. The preparing method is mild in reaction condition, easy to implement, short in reaction time, high in yield and low in cost, and mass preparation can be easily achieved.

Description

technical field [0001] The invention relates to the field of medicine and chemical industry, in particular to a 4-substituted amino-6-methoxycarbonylbenzofuro[2,3-d]pyrimidine compound and its preparation and application. Background technique [0002] Benzofuropyrimidine derivatives are a class of fused heterocyclic compounds with good biological activity, for example: N-(3-bromophenyl)-benzofuro[3,2-d]pyrimidine (structural formula A) has Inhibitory activity of epidermal growth factor receptor tyrosine kinase (J.Med.Chem.1999, 42, 5464-5474); 4-Alkylamino-8-methylsulfonylbenzofuro[3,2-d]pyrimidine -2-amine (structural formula B) is a histamine H 4 Receptor modulator with antihistamine H 4 Mediated various immune and inflammatory reactions and other activities (EP2020412A1, [P] 2009-02-04); derivatives of benzofuro[3,2-d]pyrimidin-2-one (structural formula C) can inhibit HIV The expression of -1 reverse transcriptase has better anti-HIV-1 virus activity (Bioorg. Med. Chem...

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Problems solved by technology

[0004] At present, the reported synthesis methods of benzofuropyrimidines mainly include the following: (1) Electrochemical oxidation of 3,4-dihydroxybenzoic acid and coupling of 1,3-dimethylbarbituric acid Decarboxylation reaction (J.Org.Chem., 2002, 67, 5036-5039), but this type of method requires special electrode materials, long reaction time, and narrow substrate applicability; (2) o-methoxyarylboronic acid compounds Suzuki coupling reaction with aminopyrimidines (WO2007 / 090852A1, [P] 2007-08-16), but this method requires expensive Pd metal complexes to catalyze, the reaction conditions are harsh, and the production cost is high; (3) base Catalyzes the coupling ring closure series reaction of o-cyanophenol and α-bromocarbonyl compound (Bioorg.Med.Chem.Lett., 2013,23,2775-2780), but the reaction reagents of this method are highly toxic and cause serious environmental pollution , and the synthetic route is longer

At present, compared with benzofuro[3,2-d]pyrimidines, there is no literature report on the synthesis method of benzofuro[2,3-d]pyrimidines, and there is no use of renewable resources for Starting materials, related reports on the preparation of 4-substituted amino-6-methoxycarbonylbenzofuro[2,3-d]pyrimidines by metal-free catalysis

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