Hydrazine → 3-Amino-4-methylbenzohydrazide

To a solution of 3-amino-4-methyl-benzoic acid ethyl ester (10 g) in EtOH (25 mL) was added anhydrous hydrazine (20 mL) dropwise over 45 min at rt. The reaction was stirred at rt. overnight, then concentrated to afford 3-amino-4-methyl-benzoic acid hydrazide (10 g) as a yellow solid. The hydrazide (500 mg) was dissolved in THF (5 mL) and TMS-isocycanate (0.41 mL) was added. After 2-3 h, HPLC analysis indicated 50-60% conversion of the hydrazide. No further conversion was found after 3 days at rt. Evaporation of the THF was followed by addition of 1 N NaOH (2 mL) and the solution was heated to 100° C. overnight. LCMS analysis indicated the desired oxo-triazole to be present along with the carboxylic acid corresponding to hydrolysis of the hydrazide. The solution was neutralized with 1N HCl and the crude product collected by filtration. The crude 5-(3-amino-4-methyl-phenyl)-2,4-dihydro-[1,2,4]triazol-3-one (100 mg) was dissolved in DMF (1 mL) along with 4-chloro-5-methyl-pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester (119 mg), and the solution was heated to 55° C. overnight. The product was purified by reverse phase preparative HPLC to afford Example 51 as a white solid (151 mg, TFA, hydrate), HPLC ret. t. (min): 2.33, MW: 379.4, LCMS[M+H2O+H]+=398.