反应详情

6-[(Methyloxy)carbonyl]-2-pyridinecarboxylic acid (272 mg, 1.500 mmol) was dissolved in dichloromethane (50 mL) and stirred under argon at room temperature. Then HBTU (569 mg, 1.500 mmol) was added followed by 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine hydrochloride (510 mg, 1.5 mmol) and then the TEA (0.418 mL, 3.00 mmol). The mixture was stirred under argon overnight. The solvent was evaporated, and the residue partitioned between EtOAc (75 mL) and water (25 ml). The organic phase was washed with water (3×25 mL), brine, dried over anhydrous sodium sulfate, filtered and evaporated to give the crude residue. It was purified by CombiFlash on a 12 gram silica column eluted with 60-100% EtOAc in hexane. Product fractions were combined and concentrated to give methyl 6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylate (609 mg, 1.305 mmol, 87% yield) as a white solid. LC-MS m/z 467 (M+H)+, 0.74 min (ret time).

1. stirringThe mixture was stirred under argon overnight
2. customThe solvent was evaporated
3. customthe residue partitioned between EtOAc (75 mL) and water (25 ml)
4. washThe organic phase was washed with water (3×25 mL), brine
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. customevaporated
8. customto give the crude residue
9. customIt was purified by CombiFlash on a 12 gram silica column
10. washeluted with 60-100% EtOAc in hexane
11. concentrationconcentrated