Chloroacetyl chloride → tert-butyl(1-(4-(2-oxo-7-phenyl-1-(tetrahydro-2H-pyran-4-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate

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Reaction Steps

To a solution of tert-butyl(1-(4-(6-hydroxy-3-phenyl-5-((tetrahydro-2H-pyran-4-yl)amino)pyridin-2-yl)phenyl)cyclobutyl)carbamate (240 mg, 0.46 mmol) in dry THF (11 mL) was added N,N-diisopropylethylamine (0.41 mL, 2.32 mmol). 2-chloroacetyl chloride (0.19 mL, 2.32 mmol) was added dropwise at 0 C. The resulting mixture was stirred overnight at room temperature. A saturated solution of NaHCO3 (8 mL) was added and the mixture was stirred under reflux for 2 hours. After allowing to cool to room temperature, the organic phase was separated and the aqueous phase extracted with AcOEt (3×10 ml). The combined organic phases were dried over Na2SO4 and concentrated to dryness under reduced pressure. The resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 50% EtOAc in cyclohexane) to give the title compound (154 mg, 59%). 1H NMR (500 MHz, CDCl3): 7.45 (1H, s), 7.24-7.22 (5H, m), 7.19-7.17 (2H, m), 7.14-7.12 (2H, m), 4.94 (1H, s), 4.71 (2H, s), 4.60-4.55 (1H, m), 4.07-4.03 (2H, m), 3.45 (2H, t), 2.63-2.54 (2H, m), 2.52-2.20 (4H, m), 2.00-1.95 (1H, m), 1.79-1.65 (3H, m), 1.40-1.10 (9H, br).

Provenance & Evidence