6-Methylpyrimidin-4-amine → HCID 86687647, compound

Participants

Reaction Steps

A vial was charged with perfluorophenyl 1-(3′,5′-difluoro-3-methoxy-[1,1′-biphenyl]-4-yl)isoquinoline-6-sulfonate (INTERMEDIATE KKKKK; 63.5 mg, 0.107 mmol), 6-methylpyrimidin-4-amine (12.26 mg, 0.112 mmol), and THF (535 μl). The vial was cooled in an ice-water bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (225 μl, 0.225 mmol) was added. After 20 min of stirring, the mixture was loaded directly onto a silica gel loading column. The column was eluted onto a pre-equilibrated 12-g Redi-Sep Gold column with 0-10% MeOH/DCM to give an orange solid. This solid was resubjected to chromatography on silica gel (12-g Redi-Sep Gold column, 4.5% MeOH/DCM) to give 1-(3′,5′-difluoro-3-methoxy-[1,1′-biphenyl]-4-yl)-N-(6-methylpyrimidin-4-yl)isoquinoline-6-sulfonamide (26.22 mg, 0.051 mmol, 47.3% yield) as a light-pink solid. 1H NMR (400 MHz, DMSO-d6) δ=13.48-12.42 (m, 1H), 8.75-8.62 (m, 2H), 8.47 (s, 1H), 8.11 (d, J=5.6 Hz, 1H), 7.95 (d, J=9.1 Hz, 1H), 7.75 (d, J=8.7 Hz, 1H), 7.63 (d, J=6.9 Hz, 2H), 7.57-7.48 (m, 2H), 7.46-7.40 (m, 1H), 7.34-7.23 (m, 1H), 7.06-6.86 (m, J=17.2 Hz, 1H), 3.77 (s, 3H), 2.31 (s, 3H). m/z (ESI) 519.0 (M+H)+.

Provenance & Evidence