1H-1,2,4-Triazole → 7-(3-bromophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)-imidazo[5,1-f][1,2,4]triazin-2-amine

Participants

Reaction Steps

To a solution of 3-bromo-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide (Intermediate 18) (490 mg, 1.0 mmol) and 1,2,4-triazole (210 mg, 3.0 mmol) in pyridine (10 mL) was added phosphorus oxychloride (0.14 mL, 1.5 mmol). The mixture was stirred at room temperature for 24 hours. The excess phosphorus oxychloride was quenched with methanol and ammonium hydroxide. The product was extracted into ethyl acetate (100 mL) and washed with 0.1N hydrochloric acid (3×50 mL). The solution was dried with magnesium sulfate and filtered. Silica gel (2.5 g) was added, followed by evaporation of the volatiles under reduced pressure. The pre-adsorbed solids were loaded into a solid loading cartridge and subjected to a gradient elution using ethyl acetate:hexanes (25:75) to ethyl acetate:hexanes (75:25) using a RediSep silica gel cartridge (12 g; ISCO). The appropriate fractions were combined and concentrated under reduced pressure to give 7-(3-bromophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)-imidazo[5,1-f][1,2,4]triazin-2-amine (0.23 g) as a yellow solid. 1H NMR (CD3OD): δ9.01 (s, 1H) 8.51 (dd, J=1.9, 1.6 Hz, 1H), 8.33 (ddd, J=7.9, 1.4, 1.1 Hz, 1H), 7.57 (ddd, J=7.9, 1.9, 1.1 Hz, 1H), 7.38 (dd, J=8.1, 7.9 Hz, 1H), 6.99 (s, 2H), 3.76 (s, 6H), 3.75 (s, 3H), 2.56 (s, 3H). MS m/z 470, 472 (M+1, M+3).

Provenance & Evidence