4-Aminopyrimidine → HCID 86687629, compound

Participants

Reaction Steps

A round-bottom flask was charged with perfluorophenyl 1-(4-chloro-2-methylphenyl)isoquinoline-6-sulfonate (INTERMEDIATE DDDDD, 189 mg, 0.378 mmol), pyrimidin-4-amine (39.6 mg, 0.416 mmol), and THF (1891 μl) to give a clear, lightly-colored solution. The flask was cooled in an ice-bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (794 μl, 0.794 mmol) was added drop wise over 30 s to give a yellow suspension. After 15 min, the mixture was quenched by the addition of TFA (0.3 mL), and then concentrated. The residue was concentrated from DCM then from MeOH. The residue was then purified by chromatography on silica gel (12-g Redi-Sep Gold column, 5-10% MeOH/DCM). Fractions containing product were combined and concentrated. The residue was taken up in DCM and filtered. The collected solid was washed with DCM (3×), then dried under a stream of N2 (g) for 20 min to give 1-(4-chloro-2-methylphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (70.2 mg, 0.171 mmol, 45.2% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.72 (d, J=5.7 Hz, 2H), 8.58 (br. s., 1H), 8.26 (br. s., 1H), 8.16 (d, J=5.4 Hz, 1H), 8.00-7.94 (m, 1H), 7.69 (d, J=8.3 Hz, 1H), 7.53 (d, J=2.0 Hz, 1H), 7.46-7.40 (m, 1H), 7.36-7.30 (m, 1H), 7.05 (s, 1H), 1.98 (s, 3H). m/z (ESI) 411.2 (M+H)+.

Provenance & Evidence