Hydrochloric Acid → n-{5-[n'-(4-Chlorophenyl)-n'-methylhydrazinocarbonyl]-1h-thieno[2,3-c]pyrazol-3-yl}-4-(4-methylpiperazin-1-yl)benzamide

Participants

Reaction Conditions

Reaction Steps

Ethyl 1-(1-ethoxyethyl)-3-[4-(4-methylpiperazin-1-yl)benzoylamino]-1H-thieno[2,3-c]pyrazole-5-carboxylate (0.5 g, 1.03 mmol, 1 eq.) and toluene (5 mL) are placed in a dry 20 mL round-bottomed flask under argon. The suspension is stirred at a temperature in the region of 0° C., and a solution of trimethylaluminum (1.54 mL, 3 eq.) is then added dropwise to avoid rises in temperature. Once the addition is complete, the mixture is left stirring for 30 minutes at a temperature in the region of 25° C., followed by addition of a solution of N-(4-chlorophenyl)-N-methylhydrazine (0.480 g, 3.09 mmol, 3 eq.). The reaction mixture is then heated to a temperature in the region of 50° C. until the starting material has totally disappeared. After 2 hours 30 minutes, the mixture is allowed to return to a temperature in the region of 25° C., and is then diluted with ethyl acetate. A few drops of monopotassium phosphate are added thereto, until the evolution of gas has ceased, and the mixture is then left stirring for one hour. The solvent is then evaporated off and then the residue is dissolved in a mixture of dichloromethane and methanol. This solution is placed directly onto silica gel for purification by chromatography, eluting at the start with a methanol/dichloromethane mixture (10/90 by volume). Ethoxyethyl intermediate: LC/MS RT=3.41 min.; M+H+ 596.1. M−H− 594.2. After evaporation, the solid obtained is placed directly in 5 mL of tetrahydrofuran and 2 mL of 5 N hydrochloric acid at a temperature in the region of 50° C. N-{5-[N′-(4-Chlorophenyl)-N′-methylhydrazinocarbonyl]-1H-thieno[2,3-c]pyrazol-3-yl}-4-(4-methylpiperazin-1-yl)benzamide is thus obtained (119 mg, 22% for the two steps). MS: ES m/z=524

Provenance & Evidence