Hydrochloric Acid → 3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propan-1-ol

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Reaction Steps

A solution of 4-(1,2,4-triazol-4-yl)phenylhydrazine (prepared as described in WO 94/03446, Example 1) (25 g, 143 mmol) in dioxan (250 ml) was treated with dihydropyran (24 g, 286 mmol) followed by 1 M hydrochloric acid (150 ml) and heated at reflux for 18 hours. The reaction mixture was evaporated with toluene then reevaporated. Inorganic solids were removed by treating the residue with a mixture of methanol and acetonitrile. The mother liquors were purified by column chromatography on silica using dichloromethane:methanol (9:1→4:1) as the eluant. The compound was recrystallised from acetonitrile to afford the title compound as a white solid (10.24 g, 30%), mp 205-207° C. δ (360 MHz, d6 -DMSO) 1.81 (2H, quintet, J=7Hz, CH2), 2.75 (2H, t, J=8Hz, CH2), 3.46 (2H, dt, J1 =6Hz, J2 =5Hz, CH2), 4.43 (1H, t, J=5Hz, OH), 7.26 (1H, d, J=2Hz, AR--H), 7.29 (1H, dd, J1 =9Hz, J2 =2Hz, Ar--H), 7.47 (1H, d, J=9Hz, Ar--H), 7.77 (1H, d, J=2Hz, Ar--H), 9.01 (2H, s, Triazole-H), 11.05 (1H, br s, indole NH). MS, CI+, m/z for (M+H)+ =243.

Provenance & Evidence