Lithium Hexamethyldisilazide → 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(5-methyl-4-(trifluoromethyl)thiazol-2-yl)-1H-indole-6-sulfonamide

Participants

Reaction Steps

A flask was charged with perfluorophenyl 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)-phenyl)-1H-indole-6-sulfonate (INTERMEDIATE E) (44.48 mg, 0.074 mmol), 5-methyl-4-(trifluoromethyl)thiazol-2-amine (17.51 mg, 0.096 mmol) and THF (0.5 mL). The flask was cooled in an ice bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (185 μl, 0.185 mmol) was added dropwise to give an orange solution. The mixture was stirred for 1 h, then an additional portion of the base solution (0.08 mL) was added. After 20 min, the cooling bath was removed. The mixture was stirred for an additional 20 min, then an additional portion of 5-methyl-4-(trifluoromethyl)thiazol-2-amine (10 mg) was added. The mixture was stirred for 20 min, then was quenched with AcOH (0.1 mL) and concentrated from MeOH/DCM. The crude product was purified by chromatography on silica gel (0 to 5% MeOH/DCM) to give 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(5-methyl-4-(trifluoromethyl)thiazol-2-yl)-1H-indole-6-sulfonamide (12.27 mg, 0.020 mmol, 27.7% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ=8.01 (d, J=1.5 Hz, 1 H), 7.94-7.82 (m, 2 H), 7.77 (d, J=0.9 Hz, 1 H), 7.61 (d, J=8.5 Hz, 1 H), 7.50 (dd, J=1.7, 8.5 Hz, 1 H), 7.37 (d, J=1.9 Hz, 1 H), 7.24 (s, 1 H), 6.34 (d, J=1.9 Hz, 1 H), 3.82 (s, 3 H), 3.24 (s, 3 H), 2.40-2.35 (m, 3 H). m/z (ESI) 600.2 (M+H)+.

Provenance & Evidence