Hydrochloric Acid → HCID 178425593, compound

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 1-(4-bromo-1H-imidazol-2-yl)-2-(7-methyl-2-((2(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethylcarbamate (19.0 mg, 0.035 mmol) was dissolved in a minimum amount of ethyl acetate, and treated with hydrochloric acid (4 N in dioxane, 1.0 mL) (1.0 mL). The mixture was stirred under nitrogen for 3 days. 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 (6.2 mg, 0.038 mmol, 1.1 equiv) and N′N-diisopropylethylamine (25.0 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 (10.1 mg, 0.038, 1.1 equiv). The mixture was stirred at room temperature overnight. The solvent was evaporated and the residue purified by column chromatography to afford 7.3 mg, (36%, 2 steps). 1H-NMR (CD3OD, 500 MHz) δ 1.50-1.71 (m, 4H), 2.55 (s, 3H), 2.74-2.93 (m, 2H), 3.16-3.25 (m, 2H), 4.03-4.20 (m, 4H), 4.78 (m, 1H), 5.12-5.19 (m, 1H), 6.63 (d, J=7.9, 1H), 6.94 (d, J=7.9, 1H), 6.94-7.00 (m, 2H), 7.04 (s, 1H), 7.12 (s, 1H), 7.12 (d, J=7.3, 1H), 7.16 (dd, J=7.6, 7.6, 1H), 7.40 (s, 1H), 7.99 (s, 1H). Mass spec.: 577.67 (MH)+.

Provenance & Evidence