Hydrochloric Acid → 4-((1-(3-fluorobenzyl)-1H-indazol-5-yl)amino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A flask equipped with mechanical stirrer was charged with 4-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-5-methyl-pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid ethyl ester (19) (1 equiv), THF (4 volumes) and MeOH (2.5 volumes). The suspension was cooled to 5 C and 50% NaOH (5.3 equiv.) solution was slowly added maintaining the temperature below 15° C. The resulting solution was warmed to 60° C. for 4 h, and then cooled to 25° C. THF (7 volumes) was charged to the reaction and concentrated HCl (9.95 equiv.) was slowly added maintaining the temperature below 35° C. to pH 3. The resulting slurry was stirred at ambient temperature overnight, and then filtered. The filter cake was washed with H2O (3×5 volumes) and dried on the filter for 1 h. The filter cake was washed with heptane (1×1 volume) and dried under vacuum at 50° C. to afford the product in 88% yield as an off-white solid.

Provenance & Evidence