Cesium carbonate → tert-Butyl 4-(1-(cyclopropylmethyl)-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)benzylcarbamate

Participants

Reaction Conditions

Reaction Steps

In a 15 mL reaction tube was added 6-bromo-1-(cyclopropylmethyl)-7-phenyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one (80 mg, 0.223 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylcarbamate (89 mg, 0.267 mmol) and CESIUM CARBONATE (363 mg, 1.114 mmol) in a mixture of 1,4-Dioxane (3341 NI) and water (1114 μl) to give a colourless solution. This was degassed by bubbling nitrogen for 15 minutes, followed by the addition of PdC12(dppf)-CH2Cl2Adduct (36.4 mg, 0.045 mmol) and degassing for a further 5 minutes. The reaction mixture was heated to 50° C. under a nitrogen atmosphere for one hour. LC-MS analysis showed reaction completion. The reaction mixture was allowed to cool to room temperature, diluted with water (5 mL) and extracted into ethyl acetate (3×5 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated to dryness under reduced pressure to give an off-white solid. The resulting residue was purified via Biotage (15-85% cyclohexane:EtOAc; 10 g column) to give the title compound (80 mg, 74%). 1H NMR (500 MHz, CDCl3): 7.39 (1H, s), 7.32-7.26 (5H, m), 7.20-7.18 (2H, dd), 7.12-7.10 (2H, d), 4.89 (2H, s), 4.80 (1H, br), 4.27 (2H, s), 3.87-3.86 (2H, d), 1.48-1.45 (9H, br), 1.18-1.15 (1H, m), 0.60-0.56 (2H, m), 0.48-0.45 (2H, m).

Provenance & Evidence