Method for synthesizing nucleoside antiviral drug intermediate thiopyrimidone derivatives

Abstract

The invention provides a method for synthesizing a thiopyrimidone compound shown as a formula (III). The method includes: in an inertial atmosphere, adding a compound shown as a formula (I), a compound shown as a formula (II), a phase transfer catalyst, a cocatalyst and alkali into a solvent, adding an additive serving as a reaction promoter under a condition of stirring, performing reflux stirring reaction for 5-12h at 60-100 DEG C, filtering to remove the solvent after reaction is finished, performing silica gel column chromatography separation, collecting eluent, and removing elution solvent to obtain the compound shown as the formula (III) in the specification, wherein R1 and R2 are H, C1-C6 alkyl groups, C1-C6 alkoxy groups or halogen substituted C1-C6 alkyl groups respectively and independently, X refers to halogen, and n is an integer in a range of 1-6, R3 is halogen, an acyl group with 1-6 carbon atoms, an acyloxy group with 1-6 carbon atoms, a phenyl group, a substituted phenyl group or a substituted hexaceteroary group. By proper selection and combination of alkalis, solvents, catalysts and promoters, synergistic effects are achieved, high-yield high-purity products can be obtained, O-isomer generation is avoided, and the method has an extensive application potential in the field of nucleotide medical intermediate synthesis.

Description

technical field [0001] The invention relates to a method for synthesizing nucleoside drug intermediate compounds, more specifically to a method for synthesizing thiopyrimidinone compounds, and belongs to the fields of organic synthesis and pharmaceutical intermediate synthesis. Background technique [0002] Hepatitis and human immunodeficiency virus (HIV) are major diseases that seriously threaten human health and are prevalent worldwide. At present, most effective drugs for treating the above diseases are nucleoside drugs. Therefore, natural product drugs based on the modification of natural product deoxynucleic acid DNA and nucleic acid RNA monomer nucleosides have been widely used in the design and synthesis of antiviral drugs. So far, there are more than 50 nucleosides Drugs are widely used to treat diseases such as hepatitis and AIDS. Research on new synthetic methods of nucleoside compounds and their intermediates has always been a hot issue of great concern to organi...

AI Technical Summary

Problems solved by technology

This method uses a severe excess of silylation reagent, and there are obvious disadvantages in production cost and waste liquid recovery. At the same time, the purity of the product is still very poor, which cannot meet the needs of medication.

[0008] As mentioned above, although the preparation methods of various types of nucleoside compounds have been disclosed in the prior art, these methods still cannot overcome the isomer by-products brought about by the alkylation reaction of nucleoside compounds, and cannot meet the requirements of pharmaceutical synthesis. field production needs

This is mainly due to the insufficient purity caused by the existence of isomers in its intermediates, which in turn leads to problems such as cumbersome post-processing and increased production costs.

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