Sodium Carbonate → 5-(2-Chloro-4-fluorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of (2-chloro-4-fluorophenyl)boronic acid (251 mg, 1.44 mmol) and 5-bromo-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (Intermediate 4) (400 mg, 1.2 mmol) in dioxane (10 mL) under nitrogen was added Pd(PPh3)4 (69 mg, 0.06 mmol) followed by a solution of Na2CO3 (382 mg, 3.6 mmol) in water (2.5 mL). The reaction mixture was sealed and heated at 120° C. under microwave irradiation for 1 hour. The reaction mixture was diluted with DCM (100 mL) and washed with saturated NaHCO3(aq) (40 mL). The organic phase was separated, dried over MgSO4, and filtered. The filtrate was diluted with MeOH (10 mL) and SiliaMetS-DMT (0.61 mmol/g, 0.984 mg, 0.6 mmol) was added. The resulting suspension was stirred at room temperature for ˜18 hours then filtered. The filtrate was concentrated in vacuo to afford the crude product as a yellow/orange oil. The crude material was purified by flash chromatography using a 24 g silica cartridge running a gradient from 2-10% [2M NH3 in MeOH]/DCM to afford the title compound as a pale yellow solid (312 mg, 68% yield). LC-MS: Rt 0.97 min; MS m/z 383.4 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.03 (dd, J=8.84, 6.32 Hz, 1H), 7.65 (dd, J=9.09, 2.53 Hz, 1H), 7.36-7.43 (m, 1H), 4.34 (tt, J=12.38, 3.28 Hz, 1H), 3.00 (s, 3H), 1.62 (dd, J=12.13, 3.03 Hz, 2H), 1.43 (t, J=12.38 Hz, 2H), 1.28 (br. s., 1H), 1.20 (s, 6H), 1.08 (s, 6H).

Provenance & Evidence