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

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (129 mg, 0.620 mmol) and 5-(4-bromo-2-chlorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (250 mg, 0.563 mmol) in dioxane (4 mL) was added Pd(PPh3)4 (33 mg, 0.028 mmol), followed by a solution of Na2CO3 (179 mg, 1.69 mmol) in water (1 mL). The reaction mixture was purged with nitrogen, sealed, and heated at 80° C. for an hour under microwave irradiation. The reaction mixture was diluted with EtOAc (50 mL) and washed with saturated NaHCO3(aq) (25 mL). The organic phase was separated, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo to afford the crude product as a brown solid. The crude material was taken up in a 2:1 mixture of MeOH:DMSO (4.5 mL), passed through a syringe filter, and purified by UV-directed preparative HPLC under basic conditions (5 mM NH4OH), collecting at 335 nm to afford the title compound as a white solid (138 mg, 55% yield). LC-MS: Rt 0.90 min; MS m/z 445.3 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.32 (s, 1H), 8.02 (s, 1H), 7.99 (d, J=8.08 Hz, 1H), 7.84 (d, J=1.52 Hz, 1H), 7.67 (dd, J=8.08, 1.52 Hz, 1H), 4.36 (tt, J=12.44, 3.47 Hz, 1H), 3.88 (s, 3H), 3.01 (s, 3H), 1.62 (dd, J=11.87, 3.28 Hz, 2H), 1.43 (t, J=12.13 Hz, 2H), 1.28 (br. s., 1H), 1.21 (s, 6H), 1.09 (s, 6H). LC-MS: Rt 1.84 mins; MS m/z 444.8 M+ [Method B].

Provenance & Evidence