Perfluoro-1-butanesulfonyl fluoride → 2-(4-tert-butylphenyl)-N-{(S)-[1-(2-fluoro-1,1-dimethylethyl)-1H-1,2,3-triazol-4-yl][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}acetamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 0.02 g (0.04 mmol) 2-(4-tert-butylphenyl)-N-{(S)-[1-(2-hydroxy-1,1-dimethylethyl)-1H-1,2,3-triazol-4-yl][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}acetamide in 0.20 ml CH3CN at rt was added 0.02 ml (0.13 mmol) DIEA, 0.009 ml (0.05 mmol) N,N-diisopropylethylamine trihydrofluoride, and 0.007 ml (0.04 mmol) perfluoro-1-butanesulfonyl fluoride (PBSF). After 2 h at room temperature, 0.007 ml (0.04 mmol) PBSF was added to the reaction mixture and the reaction was heated to 45° C. After 18 h at 45° C., the reaction temperature was increased to 60° C. After 4 h at 60° C., add 0.009 ml (0.05 mmol) N,N,-diisopropylethylamine trihydrofluoride and 0.007 ml (0.04 mmol) PBSF and continue heating. After 24 h, the reaction is still incomplete. At this point, the reaction mixture was quenched with water, filtered through a plug of silica and concentrated in vacuo. Purification by preparative HPLC (5->95% CH3CN/H2O over 15 min, 0.05% added TFA, C18) afforded 0.003 g (16%) 2-(4-tert-butylphenyl)-N-{(S)-[1-(2-fluoro-1,1-dimethylethyl)-1H-1,2,3-triazol-4-yl][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}acetamide. ES-MS [M+1]+=522.3. 1H NMR (CDCl3, 400 MHz) 8.24 (d, 1H, J=2.65 Hz); 7.57 (s, 1H); 7.40-7.30 (m, 3H); 7.31-7.22 (m, 3H); 4.57-4.46 (d, 1H, J=47.2 Hz); 4.41 (q, 2H, J=8.06 Hz); 3.63 (s, 2H); 1.63 (s, 6H); 1.32 (s, 9H).

Provenance & Evidence