Dimethylformamide → 1-(2-methoxy-4-(2,2,2-trifluoroethoxy)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Participants

Reaction Conditions

Reaction Steps

A vial was charged with 1-(4-hydroxy-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (from EXAMPLE 361, STEP 1; 54 mg, 0.102 mmol), cesium carbonate (100 mg, 0.306 mmol), and DMF (511 μl). 2,2,2-Trifluoroethyl trifluoromethanesulfonate (28.0 μl, 0.204 mmol) was added and the vial was heated to 50° C. for 1 h. The mixture was diluted with water and extracted with EtOAc (3×). The combined organic extracts were concentrated. The residue was dissolved in DCM (1 mL) and TFA (1 mL), and the resulting solution was stirred overnight. The mixture was diluted with MeOH and concentrated. The residue was dissolved in EtOAc and washed with saturated aq. sodium bicarbonate solution. The aq. wash was extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (3.5% MeOH/DCM) to give 1-(2-methoxy-4-(2,2,2-trifluoroethoxy)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (32.7 mg, 0.067 mmol, 65.3% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=13.06 (br. s., 1H), 8.70-8.61 (m, 2H), 8.57 (s, 1H), 8.25 (d, J=5.6 Hz, 1H), 8.06 (d, J=5.8 Hz, 1H), 7.94 (dd, J=1.9, 8.9 Hz, 1H), 7.72 (d, J=8.9 Hz, 1H), 7.30 (d, J=8.3 Hz, 1H), 7.03 (d, J=5.1 Hz, 1H), 6.90 (d, J=2.3 Hz, 1H), 6.82 (dd, J=2.3, 8.4 Hz, 1H), 4.89 (q, J=8.9 Hz, 2H), 3.65 (s, 3H). m/z (ESI) 491.2 (M+H)+.

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