反应详情

A mixture of 1-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]cyclopropanecarboxylic acid (600 mg, 1.444 mmol), HBTU (657 mg, 1.733 mmol), Et3N (1006 μL, 7.22 mmol) and 1-(3-bromo-4-methylphenyl)methanamine (318 mg, 1.589 mmol) in DCM was stirred at room temperature overnight. The reaction mixture was quenched with saturated NaHCO3 and extracted with DCM twice. The combined organic layers were washed with brine and then concentrated under vacuum to give the crude residue. It was then purified with a Gilson HPLC (acidic conditions: 0.1% TFA in the solvents), eluting with 10 to 70% CH3CN in water at a flow rate of 20 mL/min. The product fractions were combined and washed with saturated NaHCO3 and extracted with ethyl acetate twice. The combined organic layers were dried over sodium sulfate, filtered and then concentrated under vacuum to give N1-[(3-bromo-4-methylphenyl)methyl]-N1-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,1-cyclopropanedicarboxamide (70 mg, 8.11%). LC-MS m/z 597 M+, 0.88 min (ret time).

1. customThe reaction mixture was quenched with saturated NaHCO3
2. extractionextracted with DCM twice
3. washThe combined organic layers were washed with brine
4. concentrationconcentrated under vacuum
5. customto give the crude residue
6. customIt was then purified with a Gilson HPLC (acidic conditions
7. wash0.1% TFA in the solvents), eluting with 10 to 70% CH3CN in water at a flow rate of 20 mL/min
8. washwashed with saturated NaHCO3
9. extractionextracted with ethyl acetate twice
10. dry with materialThe combined organic layers were dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated under vacuum