Potassium Phosphate, Tribasic → 2-(8-tert-Butyl-5-oxo-2,3-dihydro-5H-benzo[f][1,4]oxazepin-4-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzaldehyde

Participants

Reaction Conditions

Reaction Steps

2-Bromo-6-(8-tert-butyl-5-oxo-2,3-dihydro-5H-benzo[f][1,4]oxazepin-4-yl)benzaldehyde (109 mg, 0.27 mmol), 1-Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one (179 mg, 1.5 eq), XPHOS (8 mg, 0.06 eq), and potassium phosphate (115 mg, 2 eq) were taken up in n-butanol (2 mL) and water (0.5 mL) and a stream of argon was bubbled through the mixture for 10 minutes. Then the catalyst Pd(dba)2 (5 mg, 0.03 eq) was added and the reaction was placed under argon and stirred at 100° C. for 40 minutes. By TLC analysis the reaction was complete, so it was cooled to room temperature and diluted with ethyl acetate (150 mL) and water (50 mL). The layers were partitioned and then separated and the organic layer was further washed with water (3×50 mL) and then finally washed with brine (1×50 mL). The ethyl acetate layer was dried over magnesium sulfate, filtered and concentrated. Purification by Preparative Thin Layer Chromatography on silica gel eluting with 7% methanol in dichloromethane gave the title compound as an off-white powder (168 mg) (M+H)+=636.

Provenance & Evidence