Synthetic Research Of Delavirdine Mesylate

Delavirdine mesylate. a non-nucleoside analogues reverse transcriptase inhibitor, was developed by Pharmacia&Upjohn. It has been approved by FDA (USA) and used in treatment of AIDS worldwide in Cocktail therapy since 1997.Based on digestion of present references on its preparation or synthesis, a practical and non-infringement synthetic route was designed and accomplished to obtain the target drug. The feature of the designed route was not to take any chemicals which were sensitive to heat and shock or very toxic substance.One key intermediate (8), 5-nitroindole-2-carboxylic acid, was synthesized from ethyl 2-methylacetoacetate and diazonium of 4-nitroaniline via Fischer Indole Synthesis. The overall yield of (8) was 47.5% with 4 steps. By taking this method, the synthetic operations were quite safe and easily handle in comparison with original patent approach.The key intermediate (7) was synthesized by condensation of piperazine (or its mono Boc-piperazine) with 2-chloro-3-nitropyridine followed by reduction of nitro group, N-isopropylation and deprotection of Boc group. By regioselective N-alkylation on piperazine ring and following chemical reactions, delavirdine mesylate was synthesized in overall yield 14.8% based on chloride of intermediate (8).In this synthetic route some chemicals like DCC or EDC were not be used, therefore the final product delavirdine and its mesylate were easily purified.The overall yield and cost of synthesis or production is much better than that of patent method.Finally, the structure of delavirdine was comfirmed by spectrophotometric and chemical analyses like ¹H.¹³C (DEPT). HMQC. HMBC. MS, UV and elemental analysis.