2-Aminothiazole → 1-methyl-3-(2-(1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-1H-indole-6-sulfonamide 2,2,2-trifluoroacetate

Participants

Reaction Conditions

Reaction Steps

A flask containing a mixture of 2-aminothiazole (7.93 mg, 0.079 mmol), tert-butyl 4-(2-(1-methyl-6-((perfluorophenoxy)sulfonyl)-1H-indol-3-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (INTERMEDIATE O) (0.053 g, 0.075 mmol), and THF (0.503 ml) was cooled to 0° C. LHMDS (1.0M in THF) (0.151 ml, 0.151 mmol) was added dropwise and the reaction was stirred for 15 minutes at 0° C. An additional equivalent of aminothiazole was added, followed by 2 equivalents of LHMDS solution. The reaction was stirred for one hour at 0° C. The reaction was quenched with saturated ammonium chloride solution, diluted with DCM, and the layers were separated. The aqueous layer was extracted with DCM, and the combined organic layers were concentrated. The material was dissolved in DCM and TFA (0.1 ml, 1.298 mmol) was added. The reaction was stirred at 50° C. overnight. The reaction was concentrated and the material was purified via column chromatography (RediSep Gold 12 g silica gel column (Teledyne Isco, Lincoln, Nebr., gradient elution 0 to 10% MeOH:DCM) to afford 1-methyl-3-(2-(1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-1H-indole-6-sulfonamide 2,2,2-trifluoroacetate as a tan solid. m/z (ESI) 519.4 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm=12.61 (br. s., 1 H), 8.70 (br. s., 2 H), 7.99 (s, 1 H), 7.81-7.67 (m, 5 H), 7.59-7.52 (m, 2 H), 7.24 (d, J=4.8 Hz, 1 H), 6.81 (d, J=4.5 Hz, 1 H), 5.89 (br. s., 1 H), 3.95 (s, 3 H), 3.71 (br. s., 2 H), 2.98 (br. s., 2 H), 2.11 (br. s., 3 H)

Provenance & Evidence