反应详情

To 1-methyl-1H-2-indolecarboxylic acid (0.802 g, 4.58 mmol) in dichloromethane (14 mL) was added oxalyl chloride (4 mL, 45.8 mmol) and DMF (1 drop). The reaction mixture was stirred overnight. Solvent was evaporated and the residue was dissolved in Dichloromethane (5 mL). Half of the dichloromethane solution (2.5 mL) was added to a solution of trans-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.50 g, 1.145 mmol) in pyridine (6 mL) at 0° C. After 30 minutes, the solid was collected by filtration. Water was then added to the solid and the pH of the solution was adjusted to 10 with sodium hydroxide (1.0N). The aqueous was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (80:20) as mobile phase to give trans-N2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide (0.545 g, 80%). 1H NMR (DMSO-d6) δ 1.49 (m, 2H), 2.02 (m, 6H), 2.17 (s, 3H), 2.36 (m, 5H), 2.55 (m, 4H), 3.96 (s, 3H), 4.04 (s, 3H), 4.66 (m, 1H), 7.15 (m, 1H), 7.28-7.35 (m, 4H), 7.58 (d, J=8.42 Hz, 1H), 7.70 (d, J=7.96 Hz, 1H), 8.11 (d, J=8.14, 1H), 8.24 (s, 1H), 9.43 (s, 1H).

1. customSolvent was evaporated
2. dissolutionthe residue was dissolved in Dichloromethane (5 mL)
3. waitAfter 30 minutes
4. filtrationthe solid was collected by filtration
5. additionWater was then added to the solid
6. extractionThe aqueous was extracted with dichloromethane
7. washThe combined organic layer was washed with water
8. dry with materialbrine, dried over MgSO4
9. filtrationfiltered
10. customevaporated
11. customThe residue was purified by flash column chromatography