Triethylamine → 4-(azetidine-1-carbonyl)-1-methyl-N-(6-methyl-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1H-pyrazole-5-carboxamide

Participants

Reaction Conditions

Reaction Steps

To an argon purged solution of 6-methyl-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-amine hydrochloride (147 mg, 564 μmol) and triethylamine (78.6 μl, 564 μmol) in dioxane (8 ml) is added trimethylaluminum (2M solution in toluene, 705 μl, 1.41 mmol). The resulting mixture is stirred for 1 hour at 25° C., then ethyl 4-(azetidine-1-carbonyl)-1-methyl-1H-pyrazole-5-carboxylate (134 mg, 564 μmol) is added; the mixture is heated to 100° C. and stirred for 18 hours. As no conversion is detected N-ethyl diisopropylamine (246 μl, 1.41 mmol) and another portion of trimethylaluminum (2M solution in toluene, 705 μl, 1.41 mmol) are added, the mixture is stirred for 1 hours at 25° C. and then for further 20 hours at 100° C. The crude material is loaded on silica and purified by flash chromatography on a 20 g silica column using heptane/ethyl acetate 10-100% as eluent affording 4-(azetidine-1-carbonyl)-1-methyl-N-(6-methyl-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1H-pyrazole-5-carboxamide (57 mg, 24.3%) as a light yellow solid. mp.: 226-8° C. MS: m/z=416.2 (M+H+).

Provenance & Evidence