Hydrochloric Acid → N-[2-(7-methyl-1H-indazol-5-yl)-1-[1-(pyridin-2-ylmethyl)imidazol-2-yl]ethyl]-4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)-1-(1-(pyridin-2-ylmethyl)-1H-imidazol-2-yl)ethylcarbamate (35.2 mg, 0.063 mmol) was dissolved in a minimum amount of ethyl acetate, and treated with hydrochloric acid (4 N in dioxane, 1.0 mL). The mixture was stirred under nitrogen overnight. After removal of the solvents, the crude mixture was treated with diethyl ether to give a precipitate which was filtered. The resulting solid was dissolved in dimethylformamide (1.0 mL), cooled to 0° C., and treated with carbonyl diimidazole (11.0 mg, 0.066 mmol, 1.05 equiv) and diisopropylethylamine (44.0 μL, 4.0 equiv). The reaction was stirred for 5 min at 0° C., warmed to room temperature, stirred for 10 min, and treated with 3-(piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one (17.6 mg, 0.066 mmol, 1.05 equiv). The mixture was stirred at room temperature overnight. The solvent was evaporated and the residue purified by column chromatography to afford 4.6 mg (12%, 2 steps). 1H-NMR (CD3OD, 500 MHz) δ 1.48-1.65 (m, 4H), 2.03 (s, 1H), 2.45 (s, 3H), 2.69-2.82 (m, 2H), 3.99-4.16 (m, 2H), 4.19 (s, 2H), 5.24 (d, J=16.5, 1H), 6.67 (d, J=7.6, 1H), 6.80 (d, J=7.9, 1H), 6.89 (s, 1H), 6.97 (dd, J=8.2, 7.6, 1H), 7.10-7.23 (m, 5H), 7.30 (s, 1H), 7.37-7.42 (m, 1H), 7.94 (s, 1H). Mass spec.: 590.3 (MH)+.

Provenance & Evidence