Phosphorus oxychloride → HCID 66549902, compound

Participants

Reaction Steps

To a solution of 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylic acid (30 mg, 0.07 mmol) and pyrazin-2-amine (7 mg, 0.07 mmol) in pyridine (6 mL) was added POCl3 (0.2 mL, 2.19 mmol) at 0° C., the reaction mixture was stirred at room temperature for 15 hours, a sat. NaHCO3 solution was added slowly, the solvent was removed in vacuo, and water (5 mL) and methanol (3 mL) were added. The precipitate was collected by filtration and washed with water (3 mL) and methanol (3 mL) to afford 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(pyrazin-2-yl)piperidine-3-carboxamide (30 mg, 87.2%) as a brown solid. 1H NMR (300 MHz, DMSO): δ 10.87 (s, 1H), 9.62 (s, 1H), 9.30 (s, 1H), 8.83 (s, 1H), 8.39-8.33 (m, 2H), 7.61 (d, 1H, J=2.1 Hz), 7.31 (dd, 1H, J1=8.7 Hz, J2=2.4 Hz), 6.82 (d, 1H, J=8.4 Hz), 4.76 (d, 1H, J=11.4 Hz), 4.60 (d, 1H, J=12.3 Hz), 3.68 (s, 3H), 3.64 (s, 3H), 3.13 (t, 1H, J=10.8 Hz), 3.01-2.93 (m, 1H), 2.79-2.71 (m, 1H), 2.04-2.00 (m, 1H), 1.81-1.67 (m, 2H), 1.46-1.42 (m, 1H). LC-MS: 493 [M+H]+, tR=1.50 min. HPLC: 95.75% at 214 nm, 96.29% at 254 nm, tR=5.38 min.

Provenance & Evidence