Potassium Phosphate, Tribasic → HCID 46908893, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-bromo-3-(4,5-dihydro-oxazol-2-ylamino)-1-methyl-1H-pyridin-2-one (111 mg, 0.41 mmol), acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl ester (201 mg, 0.41 mmol), X-Phos (15 mg, 0.033 mmol) and potassium phosphate tribasic (174 mg, 0.82 mmol) was taken up in n-butanol/water (4:1, 8.1 mL) and vacuum degassed. Palladium(0) bis(dibenzylideneacetone) (10 mg, 0.02 mmol) was added and the mixture was vacuum degassed and then heated to 100° C. under argon atmosphere. After 3 hours the material was cooled to ambient. The material was taken up in dichloromethane (40 mL) and water (40 mL) and shaken in a separatory funnel. The dichloromethane phase was collected and washed with brine solution (40 mL). The aqueous phase was back extracted with methylene chloride (2×30 mL) and the organic phases combined, dried over magnesium sulfate, filtered and stripped. Residual n-butanol was removed on the pump/rotary evaporator. Chromatography (Preparative TLC [3 plates], 11% methanol/dichloromethane—methanol contains 5% triethylamine) provided semi-pure product. The material was chromatographed a second time (Preparative TLC [2 plates], using 12% methanol/dichloromethane—methanol contains 5% triethylamine) which provided the title compound as an off-white crystalline solid (25 mg). (M+H)+=518 m/e; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.38 (s, 9 H) 3.56 (s, 3 H) 3.69-3.83 (m, 2 H) 4.25 (t, J=8.5 Hz, 2 H) 4.29-4.36 (m, 2 H) 4.65 (m, 1 H) 7.35-7.54 (m, 5 H) 7.74 (dd, J=13.3, 1.7 Hz, 1 H) 7.87 (d, J=1.7 Hz, 1 H) 8.49 (d, J=2.6 Hz, 1 H)

Provenance & Evidence