2-Methylpyrimidin-4-amine → HCID 86687646, 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; 64.75 mg, 0.109 mmol), 2-methylpyrimidin-4-amine (12.50 mg, 0.115 mmol), and THF (546 μl) (not all the amine dissolved). The vial was cooled in an ice-water bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (229 μl, 0.229 mmol) was added. After 40 min, 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 0-5% MeOH/DCM to give 1-(3′,5′-difluoro-3-methoxy-[1,1′-biphenyl]-4-yl)-N-(2-methylpyrimidin-4-yl)isoquinoline-6-sulfonamide (28.4 mg, 0.055 mmol, 50.2% yield) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=13.32 (br. s., 1H), 8.68 (d, J=5.7 Hz, 1H), 8.62 (s, 1H), 8.17-8.03 (m, 2H), 7.95 (dd, J=1.7, 8.9 Hz, 1H), 7.74 (d, J=8.8 Hz, 1H), 7.68-7.59 (m, 2H), 7.56-7.48 (m, 2H), 7.46-7.39 (m, 1H), 7.29 (tt, J=2.2, 9.3 Hz, 1H), 6.90 (br. s., 1H), 3.77 (s, 3H), 2.35 (s, 3H). m/z (ESI) 519.0 (M+H)+.

Provenance & Evidence