2,2,2-Trifluoroethyl trifluoromethanesulfonate → (R)-tert-butyl 2-(2,6-difluorophenyl)-4-(1-methyl-5-(4-(2,2,2-trifluoroethylamino)azepan-1-yl)-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate

Participants

Reaction Steps

(R)-tert-butyl 4-(5-(4-aminoazepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-(2,6-difluorophenyl)thiazol-5-ylcarbamate (112 mg, 0.204 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (95 mg, 0.409 mmol) were dissolved in methylene chloride/DMF (1.5 mL/1.5 mL). N,N-diisopropylethylamine (132 mg, 1.02 mmol) was added and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated to remove DMF, redissolved in ethyl acetate and washed with brine. The aqueous layer was extracted with ethyl acetate 3×. Combined organic layers were concentrated and purified by flash chromatography eluted with 0 to 100% ethyl acetate in heptane to give (R)-tert-butyl 2-(2,6-difluorophenyl)-4-(1-methyl-5-(4-(2,2,2-trifluoroethylamino)azepan-1-yl)-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate (96 mg, 75%), which was deprotected by 4N HCl in dioxane and purified on reversed phase HPLC to give 197. 1H NMR (400 MHz, DMSO) δ 8.65 (s, 1H), 7.59-7.43 (m, 4H), 7.25 (t, J=8.7 Hz, 2H), 3.64 (s, 3H), 3.24-3.01 (m, 6H), 2.81 (s, 1H), 2.14 (d, J=6.1 Hz, 1H), 1.96-1.74 (m, 3H), 1.65-1.48 (m, 3H). MS (ESI) m/z: 530.2 [M+H+].

Provenance & Evidence