Acetic Acid → HCID 86664206, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of hydroxylamine hydrochloride (2.0 g, 29 mmol) in methanol (10.0 mL) was heated at 90° C. under a dry nitrogen atmosphere until homogeneous. To this heated solution was added a solution of potassium hydroxide (2.85 g, 50.8 mmol) in methanol (6.0 mL). A precipitate formed on mixing. After heating at 90° C. for 30 minutes, the mixture was cooled to rt and the solids were allowed to settle. The resulting solution was assumed to contain 1.7 M hydroxylamine.potassium salt and was carefully removed by syringe to exclude solids. An aliquot of the above solution (2.0 mL, 3.5 mmol) was added to a solution of methyl 4-oxo-3-(2-phenylpropan-2-yl)-3,4-dihydroquinazoline-6-carboxylate (0.11 g, 0.35 mmol) in methanol (0.75 mL) and DMF (0.50 mL). After stirring for 4 h at rt, excess reagent was quenched by the addition of acetic acid (0.2 mL, 3.5 mmol). The mixture was concentrated to dryness and the residue was twice co-evaporated with toluene. The crude product was purified by preparative HPLC to afford N-hydroxy-4-oxo-3-(2-phenylpropan-2-yl)-3,4-dihydroquinazoline-6-carboxamide (84 mg, 75%). LC-MS: (FA) ES+ 324; 1H NMR (400 MHz, DMSO) δ 11.25 (s, 1H), 9.11 (s, 1H), 8.72 (s, 1H), 8.36 (d, J=1.9 Hz, 1H), 8.14 (dd, J=8.5, 2.1 Hz, 1H), 7.76 (d, J=8.5 Hz, 1H), 7.34-7.14 (m, 5H), 1.96 (s, 6H).

Provenance & Evidence