反应详情

A mixture of 5-(3-aminopyrrolidin-1-yl)-N-(3,4-dimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine hydrochloride (82 mg, 0.2 mmol), 2-oxoindoline-6-carboxylic acid (36 mg, 0.2 mmol), EDCI (76 mg, 0.4 mmol) and N-methylimidazole (50 mg, 0.6 mmol) in 5 mL of DCM was stirred at room temperature for 16 hours. The mixture was washed with water (4 mL), The organic layer was dried over Na2SO4. After filtration and concentration, the residue was purified by preparative TLC (Silica gel, 20 cm×20 cm, separated by EtOAc, eluted by DCM:MeOH=1:20, v/v) to give N-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-yl)-2-oxoindoline-6-carboxamide (25 mg, 23.5%). 1H NMR (300 MHz, DMSO): δ 10.52 (s, 1H), 9.56 (s, 1H), 8.81 (s, 1H), 8.61 (d, 1H, J=6.3 Hz), 7.90 (brs, 1H), 7.48-7.46 (m, 2H), 7.28-7.25 (m, 2H), 6.93-6.90 (m, 1H), 4.54 (brs, 1H), 3.77-3.34 (m, 11H), 2.50-2.34 (m, 1H), 2.07-1.99 (m, 2H). LC-MS: 532 [M+H]+, 530 [M−H]−, tR=1.35 min. HPLC: 97.39% at 214 nm, 97.05% at 254 nm, tR=4.54 min.

1. washThe mixture was washed with water (4 mL)
2. dry with materialThe organic layer was dried over Na2SO4
3. filtrationAfter filtration and concentration
4. customthe residue was purified by preparative TLC (Silica gel, 20 cm×20 cm, separated by EtOAc, eluted by DCM:MeOH=1:20, v/v)