Sodium Carbonate → 5-(2-Methoxy-4-(1H-pyrazol-5-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 suspension of (1H-pyrazol-5-yl)boronic acid (14 mg, 0.139 mmol) and 5-(4-chloro-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (50 mg, 0.127 mmol) in dioxane (1 mL) was added Pd(PPh3)4 (7 mg, 0.006 mmol) followed by a solution of Na2CO3 (40 mg, 0.380 mmol) in water (0.25 mL). The reaction mixture was purged with nitrogen, sealed, and heated at 120° C. under microwave irradiation for 30 minutes, then again at 145° C. Additional catalyst and boronate were added and the mixture was heated for an additional 30 minutes under microwave irradiation at an increased temperature of 160° C. The reaction mixture was diluted with DCM (20 mL), washed with saturated NaHCO3(aq) (10 mL) and the organic phase was separated and concentrated in vacuo to afford the crude product as an oily residue. The crude material was purified by mass directed preparative HPLC under basic conditions (NH4OH midified) to afford the title compound as a white solid (12.5 mg, 23% yield). LC-MS: Rt 0.81 min; MS m/z 427.3 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.99 (br. s., 1H), 8.12 (d, J=8.08 Hz, 1H), 7.82 (br. s., 1H), 7.60 (s, 1H), 7.54 (d, J=6.06 Hz, 1H), 6.84 (d, J=2.02 Hz, 1H), 4.31-4.41 (m, 1H), 4.01 (s, 3H), 2.99 (s, 3H), 1.61 (dd, J=12.13, 3.54 Hz, 2H), 1.42 (t, J=12.13 Hz, 2H), 1.27 (br. s., 1H), 1.22 (s, 6H), 1.09 (s, 6H).

Provenance & Evidence