Lithium Hexamethyldisilazide → 1-chloro-N-(4-methoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide

Participants

Reaction Conditions

Reaction Steps

To a solution of N-(4-methoxybenzyl)-1,2,4-thiadiazol-5-amine (1.40 g, 6.33 mmol) in THF (42.2 mL) at −70° C. under an argon atmosphere was added lithium bis(trimethylsilyl)amide, 1.0 M solution in tetrahydrofuran (6.96 mL, 6.96 mmol) dropwise. The reaction mixture was removed from cooling and stirred for 45 min. The mixture was again cooled to −70° C. (internal temperature) to give a yellow suspension. Then solid 1-chloroisoquinoline-6-sulfonyl chloride (1.82 g, 6.96 mmol) was added in one portion. After 15 min, the mixture was warmed to room temperature and concentrated. The residue was absorbed onto a plug of silica gel and purified by chromatography through a silica gel column (80 g), eluting with a gradient of 0% to 50% EtOAc in hexane, to provide 1-chloro-N-(4-methoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)isoquinoline-6-sulfonamide (0.73 g, 1.633 mmol) as an orange solid. MS (ESI): 447.0 [M+H]+; 1H NMR (500 MHz, DMSO-d6) δ ppm 3.65 (s, 3H), 5.24 (s, 2H), 6.77 (m, J=8.66 Hz, 2H), 7.28 (m, J=8.66 Hz, 2H), 8.10 (dd, J=5.9, 10.8 Hz, 1H), 8.15 (d, J=6.4 Hz, 1H), 8.42 (d, J=8.6 Hz, 1H), 8.45 (s, 1H), 8.50 (d, J=5.56 Hz, 1H), 8.77 (d, J=1.71 Hz, 1H).

Provenance & Evidence