反应详情

To a solution of 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylic acid (70 mg, 0.17 mmol) and 5-aminoisoindolin-1-one (25 mg, 0.17 mmol) in dichloromethane (15 mL) were added the solution of 1-methyl-1H-imidazole (55 mg, 0.68 mmol) and EDCI (129 mg, 0.68 mmol) in dichloromethane (5 mL), the reaction mixture was stirred at room temperature for 24 hours, the solvent was removed in vacuo, then methanol (5 mL) was added, the precipitate was collected by filtration and washed with methanol (3 mL) to afford 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(1-oxoisoindolin-5-yl)piperidine-3-carboxamide (48 mg, 51.8%) as a brown solid. 1H NMR (300 MHz, DMSO): δ 10.29 (s, 1H), 9.64 (s, 1H), 8.84 (s, 1H), 8.38 (s, 1H), 7.96 (s, 1H), 7.64-7.53 (m, 3H), 7.33 (dd, 1H, J1=8.4 Hz, J2=1.8 Hz), 6.80 (brs, 1H), 4.81-4.63 (m, 2H), 4.33 (s, 2H), 3.68 (s, 3H), 3.59 (s, 3H), 3.14-2.92 (m, 2H), 2.65-2.60 (m, 1H), 2.04-2.00 (m, 1H), 1.81-1.69 (m, 2H), 1.49-1.45 (m, 1H). LC-MS: 545.9 [M+H]+, tR=1.42 min. HPLC: 99.69% at 214 nm, 99.44% at 254 nm, tR=4.87 min.

1. customthe solvent was removed in vacuo
2. additionmethanol (5 mL) was added
3. filtrationthe precipitate was collected by filtration
4. washwashed with methanol (3 mL)