Acetonitrile → HCID 49833482, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of 2-amino-5-bromopryimidine (65 mg, 0.37 mmol), {4-[(4-methylpiperidin-1-yl)carbonyl]-2,3,4,5-tetrahydro-1,4-benzoxazepine-7-yl}boronic acid (100 mg, 0.31 mmol) and potassium carbonate (215 mg, 1.6 mmol) in DMA (5.0 mL) and water (0.5 mL) was added dichloro[1,1-bis(diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (23 mg, 0.03 mmol). The reaction mixture was stirred at 95° C. for 2.5 hours and then partitioned between dichloromethane (10 mL) and 1M aqueous sodium hydroxide (10 mL). The organic layer was separated and washed with brine (10 mL) then dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was chromatographed on silica gel using 2% methanol in dichloromethane as eluent and the combined product containing fractions were concentrated. The residue thus obtained was taken into a minimum of acetonitrile and purified by preparative reverse phase HPLC to afford 5-{4-[(4-methylpiperidin-1-yl)carbonyl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}pyrimidin-2-amine (24 mg) as an amorphous solid. 1H NMR (400 mHz, DSMO-d6): 8.51 (s, 2H), 7.47 (d, 1H), 7.42 (dd, 1H), 6.98 (d, 1H), 6.75 (s, 2H), 4.39 (s, 2H), 4.12-4.18 (m, 2H), 3.46-3.59 (m, 4H), 2.70 (t, 2H), 1.42-1.61 (m, 3H), 1.04-1.18 (m, 2H), 0.91 (d, 3H); MS (EI) for C20H25N5O2: 368 (MH+).

Provenance & Evidence