1-Hydroxybenzotriazole hydrate → N-(2,3-dimethylpyridin-4-yl)-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxylic acid (30.0 mg, 0.110 mmol), 2,3-dimethyl-pyridin-4-ylamine (26.9 mg, 0.220 mmol), N-[3-(dimethylamino)propyl]-N-ethylcarbodiimide hydrochloride (31.7 mg, 0.165 mmol), and 1H-1,2,3-benzotriazol-1-ol hydrate (16.9 mg, 0.110 mmol) were suspended in DMF (1 ml). Diispropylethylamine (0.058 ml, 0.331 mmol) was added and the reaction mixture was allowed to stir. After 2 h, N,N-dimethylpyridin-4-amine (13.5 mg, 0.110 mmol) was added and the mixture was stirred overnight. After 16 h, the reaction mixture was heated to 60° C. for 4 h, after which additional 2,3-dimethyl-pyridin-4-ylamine (26.9 mg, 0.220 mmol) was added and the mixture was heated to 70° C. overnight. The reaction mixture was diluted in DMSO/water and filter through a 45 μm filter. The filtrate was purified by preparative HPLC Reverse phase (C-18), eluting with Acetonitrile/Water+0.05% TFA to give a solid that was contaminated with trace impurities. Additional purification by column chromatography on silica gel (methanol/ethyl acetate gradient) afforded (N-(2,3-dimethylpyridin-4-yl)-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide. 1H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H); 8.83 (s, 1H); 8.41 (s, 1H); 8.37 (s, 1H); 8.19 (d, 1H); 8.10 (s, 1H); 7.82 (d, 1H); 7.28 (s, 1H); 4.13 (s, 3H); 3.88 (s, 3H); 2.47 (s, 3H); 2.24 (s, 3H). LRMS (ESI) calculated for C20H21N6O2 [M+H]+, 377.2; found 377.2.

Provenance & Evidence