Pyrazole → 5-(2-Chloro-4-(1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

Participants

Reaction Steps

Cs2CO3 (128 mg, 0.392 mmol) was added to a stirred solution of 5-(2-chloro-4-fluorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (50 mg, 0.131 mmol) and 1H-pyrazole (13 mg, 0.196 mmol) in DMF (1.3 mL). The reaction mixture was stirred at room temperature for 4 days then warmed to 60° C. and stirred for an additional 18 hours. The reaction mixture was diluted with DCM (10 mL), filtered through celite, and the DCM was removed in vacuo to afford the crude product as a pale brown liquid. The crude material was purified by UV directed preparative HPLC under acidic conditions (formic acid modified), collecting at 324 nm. The product containing fractions were combined and loaded onto a 1 g SCX cartridge (pre-wet with MeOH). The cartridge was washed with MeOH (10 mL) then flushed with 10% DCM in [7M NH3 in MeOH] (10 mL). The DCM/MeOH/NH3 was removed in vacuo to afford the title compound as a clear glass-like solid (37 mg, 66% yield). LC-MS: Rt 0.97 min; MS m/z 431.5 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.67 (d, J=2.53 Hz, 1H), 8.14 (dd, J=5.56, 3.03 Hz, 2H), 7.97-8.02 (m, 1H), 7.83 (d, J=1.52 Hz, 1H), 6.64-6.60 (m, 1H), 4.37 (tt, J=12.25, 3.16 Hz, 1H), 3.02 (s, 3H), 1.63 (dd, J=12.13, 3.03 Hz, 2H), 1.45 (t, J=12.13 Hz, 2H), 1.21 (s, 6H), 1.09 (s, 6H).

Provenance & Evidence