2,4-diamino quinazolines compounds and synthesis method thereof

Abstract

The invention discloses 2, 4-diamino-quinazoline compounds and a green chemical synthesis method thereof. The synthesis method is that: multi-halogeno-m-Phthalodinitrile and guanidine salt take a ring-closing reaction, so as to obtain the compounds of Formula (IV); the produced compounds are reacted with nucleophile Nu- to obtain the compounds of Formula (I) which have potential medical activity. The novelty of the invention is that the synthesis of the compounds of Formula (IV) adopts the green chemical synthesis method and is realized under the condition of non-solvent and in the way of an ordinary thermostatic oven, oil bath or microwave radiation heating, thus the synthesis method is simple with little pollution to the environment and high and stable yield. In addition, the invention provides a route for synthesizing the 2, 4 -amino-quinazoline compounds of Formula (I) and (IV) with the potential medical activity and synthesizes a series of new 2, 4 -amino-quinazoline compounds of Formula (I) and (IV).

Description

Technical field [0001] The invention relates to 2,4-diaminoquinazoline compounds with potential drug activity and their synthesis methods. Background technique [0002] 2,4-Diaminoquinazoline compounds are a class of heterocyclic compounds with anti-HIV, anti-tumor, spinal muscular atrophy and other drug activities. For example: Trimetrexate (English name: Trimetrexate, abbreviated as TMQ), Pelitrine (English name: Piritrexim, abbreviated as PTX), etc. are non-nucleoside reverse transcriptase inhibitors, used in the treatment of human immunodeficiency virus (HIV) Acquired immunodeficiency syndrome (AIDS) has attracted much attention due to its high efficiency, low toxicity, and high selectivity (Masur H. et al. J. Infect. Dis. 1993, 167, 1442; Falloon J . et al. Clin. Res. 1990, 38, 361A; Das, K. et al. J. Med. Chem. 2004, 47, 2550-2560). In particular, it has recently been discovered that these compounds have strong drug activity against spinal muscular atrophy, which has become...

AI Technical Summary

Problems solved by technology

[0004] In the synthesis process of 2,4-diaminoquinazoline compounds, the synthetic method similar to the early report of the compound of formula (I) is: by reacting the substrate in DME (N, N-dimethylacetamide) at 145 ° C It was prepared by stirring and refluxing with guanidine carbonate for 3.5 hours. Due to the traditional solvent method of heating synthesis, not only the use of organic solvents causes environmental pollution, but also the product post-treatment process is complicated, and it is difficult to remove the solvent during the process. In addition, the reaction temperature Relatively high and low synthetic yields are a series of problems

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