Dimethylformamide → 1-(4-isobutoxy-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Participants

Reaction Steps

A vial was charged with 1-(4-hydroxy-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (38.07 mg, 0.072 mmol), cesium carbonate (70.4 mg, 0.216 mmol), and DMF (360 μl). Within a few minutes, a deep red solution formed. 1-iodo-2-methylpropane (16.58 μl, 0.144 mmol) was added. The vial was sealed and lowered into a 50° C. heating bath. After 2 h, additional portions of cesium carbonate (70.4 mg, 0.216 mmol) and 1-iodo-2-methylpropane (16.58 μl, 0.144 mmol) were added. The mixture was heated for another 1 h, then it was cooled, diluted with water, and extracted with EtOAc (3×). The combined organic extracts were concentrated. The residue was taken up in DCM (1 mL). The mixture was cooled in an ice-bath for 5 min, then TFA (0.4 mL) was added drop wise. The ice-bath was then removed and an additional portion of TFA (0.4 mL) was added. The mixture was stirred overnight, then was diluted with MeOH and concentrated. The residue was dissolved in DCM and saturated aq. sodium bicarbonate solution was added. The layers were separated, and the aq. layer was extracted with DCM (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 50-100% EtOAc, then 10% MeOH/DCM) to give 1-(4-isobutoxy-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (29.3 mg, 0.063 mmol, 88% yield) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=13.02 (br. s., 1H), 8.69-8.51 (m, 3H), 8.25 (br. s., 1H), 8.04 (s, 1H), 7.95-7.87 (m, 1H), 7.75 (d, J=8.9 Hz, 1H), 7.23 (d, J=8.3 Hz, 1H), 7.04 (br. s., 1H), 6.74 (d, J=2.2 Hz, 1H), 6.69 (dd, J=2.2, 8.3 Hz, 1H), 3.86 (d, J=6.7 Hz, 2H), 3.63 (s, 3H), 2.08 (quind, J=6.6, 13.2 Hz, 1H), 1.03 (d, J=6.7 Hz, 6H). m/z (ESI) 465.2 (M+H)+.

Provenance & Evidence