4-Aminopyrimidine → 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

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Reaction Steps

A round bottom flask was charged with perfluorophenyl 4-(2-cyano-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (INTERMEDIATE AB, 46.12 mg, 0.084 mmol), pyrimidin-4-amine (11.95 mg, 0.126 mmol), and THF (1 mL) to give a clear, colorless solution. The flask was cooled in a dry ice-acetone bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (176 μL, 0.176 mmol) was added dropwise over 30 s to give a light-yellow solution. After 5 min, the flask was lowered into an ice bath for 1 h. Glacial acetic acid (2 drops) was added, and the mixture was concentrated under a vacuum. The product was purified by chromatography on silica gel (12 g column with 0 to 10% MeOH/DCM) to give 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (25.2 mg, 0.055 mmol) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.10 (br. s., 1 H), 8.65 (s, 1 H), 8.42-8.35 (m, 2 H), 8.09 (dd, J=2.0, 8.8 Hz, 1 H), 7.74 (d, J=8.6 Hz, 1 H), 7.38 (d, J=2.1 Hz, 1 H), 7.31 (dd, J=2.2, 8.6 Hz, 1 H), 7.04 (d, J=6.0 Hz, 1 H), 6.80 (d, J=8.6 Hz, 1 H), 4.38-4.32 (m, 2 H), 3.89-3.84 (m, 2 H). m/z (ESI) 462.4 (M+H)+.

Provenance & Evidence