1H-1,2,4-Triazole → TAK-603

Participants

Reaction Steps

To a solution of 1H-1,2,4-triazole (0.558 g) in N,N-dimethylformamide (30 ml) was added sodium hydride in oil and the mixture was stirred at room temperature for 15 minutes. Then, ethyl 2-chloromethyl-4-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinoline-3-carboxylate (3.0 g) was added. The mixture was stirred at 80° C. for 1 hour, after which it was poured in water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried (MgSO4) and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography. Form the first eluate with chloroform-methanol (40:1, v/v), ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmethyl)quinoline-3-carboxylate (1.7 g, 53%) was obtained. Recrystallization from ethyl acetate-hexane provided colorless prisms, m.p. 176°-177° C.

Provenance & Evidence