Studies On A Novel Non-Nucleoside Reverse Transcriptase Inhibitor--Nevirapine

Objective: Study the synthesis of novel non-nucleoside reverse transcriptase inhibitor-----Nevirapine,and modify the synthetic route,elevate the yield.Methods:2-Hydroxy-4-methyl-3-nitropyridine was reacted with phosphorous pentachloride to give 2-chloro-4-methyl-3-nitropyridine.The latter was reduced with stannous chloride under acid condition to give 3-amino-2-chloro-4-methylpyridine.Then process Schotten-Banmann reaction with 2-chloro-nicotinoyl chloride to afford the intermediate---2-chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridinecarboxamide.The substitution action was made between the intermediate and the cyclopropylamine.Finally,the cyclization reaction was made with sodium hydride under nitrogen to afford Nevirapine, And confirm its structure by IR,1H-NMR, 13C-NMR and MS.Results:1)Decreasing the number of the thionylchloride to 1.5 time and washing 2-chloro-nicotinoyl chloride with water can success-fully eliminate the residual acid.2)The 2-chloro-4-methyl-3-nitropyridine was reduced with stannous chloride,which make easier to process,and the yield was elevated.3)Cyclization reaction is the nucleophilic substitution reaction under strong base.Conclusion:Nevirapine was prepared from 2-hydroxy-4-methyl-3-nitropyridine by six steps.The total yield was 38ï¼…. Its structure was confirmed by IR,1H-NMR, 13C-NMR and MS.