Ethanamine, 2,2,2-trifluoro- → 3-(1-(4-Fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropyl 2,2,2-trifluoroethylcarbamate

Participants

Reaction Conditions

Reaction Steps

3-(1-(4-Fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropan-1-ol (prepared from LiAlH4 reduction of methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanoate in Example 1(g)) (37 mg) in THF (1 ml) was treated with carbonyl diimidazole (29 mg, 0.176 mmol) at room temperature overnight. To the reaction solution was added 2,2,2-trifluoroethanamine (26 mg, 0.264 mmol). The reaction was heated at 50° C. for 14 hours. Additional 2,2,2-trifluoroethanamine 26 mg, 0.264 mmol) was added followed by addition of N,N-dimethylpyridin-4-amine (10 mg, 0.080 mmol), after which stirring was continued for 14 hours. The reaction was concentrated. The crude material was purified via chromatography on silica gel eluting with 10% ethyl acetate in hexane to afford the compound of Example 14 (4 mg, 10% yield). 1H NMR (400 MHz, MeOD) δ ppm 8.20 (1 H, s) 7.97 (1 H, s) 7.71 (2 H, dd, J=9.16, 4.58 Hz) 7.63 (2 H, s) 7.54 (2 H, d, J=7.12 Hz) 7.26-7.34 (4 H, m) 7.19 (1 H, t, J=7.38 Hz) 4.26 (1 H, s) 3.73-3.82 (4 H, m) 1.11 (6 H, d, J=3.05 Hz). LC/MS (m/z) 500.29 [(M+H)+]; HPLC Rt: 3.871 min.

Provenance & Evidence