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

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 1-(1-(3-fluorobenzyl)-1H-imidazol-2-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethylcarbamate (14.4 mg, 0.025 mmol) was dissolved in a minimum amount of ethyl acetate, followed by addition of hydrochloric acid (4 N in dioxane, 1.0 mL). The mixture was stirred under nitrogen for 3 days. After removing the solvents, the crude mixture was treated with diethyl ether to give a precipitate which was collected by filtration. The resulting solid was dissolved in dimethylformamide (1.0 mL). The mixture was cooled to 0° C. and treated with carbonyl diimidazole (4.7 mg, 1.1 equiv) and triethylamine (7.5 μL, 0.054 mmol). 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 (6.7 mg, 1.1 equiv). The mixture was stirred at room temperature overnight. The solvent was removed and the residue purified by column chromatography to afford 7.2 mg (47%, 2 steps). 1H-NMR (CD3OD, 500 MHz) δ 1.49-1.68 (m, 4H), 2.44 (s, 3H), 2.71-2.84 (m, 2H), 3.20-3.27 (m, 4H), 4.01-4.15 (m, 2H), 4.19 (s, 2H), 4.35 (m, 1H), 5.12 (d, J=16.2, 1H), 5.21-5.30 (m, 2H), 6.57-6.69 (m, 2H), 6.80 (d, J=7.9, 1H), 6.82 (s, 1H), 6.88-7.20 (m, 8H), 7.91 (s, 1H). Mass spec.: 607.71 (MH)+.

Provenance & Evidence