Boron tribromide → 2-(5-(piperazin-1-yl)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-1-yl)phenol

Participants

Reaction Steps

BBr3 (1M solution in heptane, 1.56 mL, 1.56 mmol) was added to a stirred, nitrogen flushed solution of tert-butyl 4-(5-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-1,3,4-thiadiazol-2-yl)piperazine-1-carboxylate (138 mg, 0.312 mmol) in DCM (6 mL) and the resulting bright yellow suspension was stirred at room temperature for 16 hours. The reaction mixture was quenched by addition of MeOH (10 mL) to give a suspension. The solid was collected by vacuum filtration, rinsed with MeOH, and re-dissolved in a mixture of DMSO and water. The solution was loaded onto a 5 g SCX cartridge (pre-wet with MeOH) and the cartridge was washed with DMSO/water (5 mL), MeOH (20 mL), then flushed with 7M NH3 in MeOH (30 mL). The MeOH/NH3 was removed in vacuo to afford the crude product as an off-white solid. The crude material was sonicated in MeOH (5 mL) and the resulting suspension filtered under vacuum to afford the title compound as an off-white solid (69 mg, 68% yield). LC-MS: Rt 0.76 min; MS m/z 329.2 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.50 (d, J=2.53 Hz, 1H), 8.03 (d, J=8.59 Hz, 1H), 7.77 (d, J=1.52 Hz, 1H), 7.52 (d, J=2.02 Hz, 1H), 7.42 (dd, J=8.59, 2.02 Hz, 1H), 6.55-6.61 (m, 1H), 3.42-3.48 (m, 4H), 2.80-2.91 (m, 4H).

Provenance & Evidence