Synthesis of P005091

Abstract

To improve the synthesis method of P005091 (1-(5-((2,3-dichlorophenyl) thio)-4-nitro-2-thienyl) ethanone), with 2-chlorothiophene as the starting material, acetyl chloride as the acetylation reagent and aluminium trichloride as the catalyst, acetyl is introduced in the 5th position of 2-chlorothiophene to get 2-acetyl-5-chlorothiophene (compound 2), and the yield is 91%; then with concentrated sulfuric acid as solvent and mixed acid as nitrating agent, 5-acetyl-2-chloro-3-nitrothiophene (compound 3) is obtained by nitration reaction with compound 2, and the yield is 64%; thioetherfication reaction of compound 3 and 2,3-dichlorobenzenethiol in DMF solution under the function of potassium carbonate takes place to obtain the target product P005091, and the yield is 76%. The structure of P005091 is confirmed by mp, 1H-NMR, 13C-NMR and MS, and the overall yield is 44%. The improved method has the advantages of low cost, simple operation, and a milder reaction condition compared with the former references, avoiding using the reagent with higher toxicity, and high yield on the premise that the product purity is assured.

Keywords

• organic synthetic chemistry
• ubiquitin-specific proteases
• thiophene
• antitumor
• synthesis
• Friedel-Crafts acylation reaction