Boron tribromide → 2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-1-yl)phenol

Participants

Reaction Steps

To a solution of 5-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (Example 1) (30 mg, 0.070 mmol) in DCM (1.5 mL) was added BBr3 (1M solution in heptane, 0.352 mL, 0.352 mmol). The resulting bright yellow suspension was stirred at room temperature for 2 h. The reaction mixture was quenched by addition of MeOH (5 mL) and the resulting solution was loaded onto a 1 g SCX cartridge (pre-wet with MeOH). The cartridge was washed with MeOH (10 mL) then flushed with 7M NH3 in MeOH (15 mL). The solvent was evaporated in vacuo. The resulting crude material was sonicated in MeOH (2 mL) and the resulting suspension was filtered under vacuum to afford the title compound as a pale yellow solid (14.9 mg, 51.4% yield). LC-MS: Rt 0.55 min; MS m/z 413.3 [M+H]+ [Method D]. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.47 (d, J=2.02 Hz, 1H), 7.99 (d, J=8.59 Hz, 1H), 7.73-7.78 (m, 1H), 7.47 (d, J=1.52 Hz, 1H), 7.36 (d, J=8.59 Hz, 1H), 6.53-6.58 (m, 1H), 4.33 (t, J=12.13 Hz, 1H), 2.99 (s, 3H), 1.58-1.69 (m, 2H), 1.47 (t, J=12.13 Hz, 2H), 1.23 (s, 6H), 1.12 (s, 6H).

Provenance & Evidence