反应详情

A flask was charged with perfluorophenyl 5-(1-benzylpyrrolidin-2-yl)naphthalene-2-sulfonate (INTERMEDIATE LL) (24.8 mg, 0.046 mmol), 1,2,4-thiadiazol-5-amine (5.64 mg, 0.056 mmol), and THF (465 μl) to give a clear, colorless solution. The flask was cooled in an ice-bath for 5 min, then lithium 2-methylpropan-2-olate (1M in hexane) (102 μl, 0.102 mmol) was added dropwise. After 1 h, the mixture was loaded directly onto a 5-g silica gel loading column with the aid of DCM. The column was dried under vacuum, then eluted onto a prequilibrated 12-g silica gel column with 0 to 10% MeOH/DCM to give 5-(1-benzylpyrrolidin-2-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (12.69 mg, 0.028 mmol, 60.6% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=8.46-8.33 (m, 2H), 8.07 (d, J=8.0 Hz, 1H), 8.02 (s, 1H), 7.97 (d, J=7.1 Hz, 1H), 7.83 (dd, J=1.9, 8.9 Hz, 1H), 7.65 (t, J=7.7 Hz, 1H), 7.34-7.21 (m, 5H), 4.62 (br. s., 1H), 3.91 (d, J=13.0 Hz, 1H), 3.24 (br. s., 4H), 1.97 (d, J=14.1 Hz, 2H), 1.86-1.72 (m, 1H); m/z (ESI) 451.4 (M+H)+.

1. customto give a clear, colorless solution
2. temperatureThe flask was cooled in an ice-bath for 5 min
3. customThe column was dried under vacuum
4. washeluted onto a prequilibrated 12-g silica gel column with 0 to 10% MeOH/DCM