反应详情

N-{[3-Bromo-4-(methyloxy)phenyl]methyl}-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-5-methyl-1,3-benzenedicarboxamide (900 mg, 1.356 mmol), (3-formylphenyl)boronic acid (203 mg, 1.356 mmol), potassium carbonate (562 mg, 4.07 mmol), and Pd(Ph3P)4 (78 mg, 0.068 mmol) were divided into 3 portions and added to three 2-5 mL Biotage microwave vials in 1,4-dioxane (3 mL) and water (1 mL). The vials were capped and the mixtures were microwaved at normal power in the Emrys Optimizer at 100° C. for 15 min. The combined crude product was partitioned between EtOAc (75 mL) and water (20 mL). The phases were separated and the organic phase was washed with water (2×20 mL), brine (20 mL), dried over anhydrous Na2SO4, filtered and evaporated to give the crude residue. It was taken up in DCM and absorbed on Isolute® Sorbent and purified by CombiFlash using an 80 g silica column eluted with 0-10% MeOH/DCM. The product fractions were combined and concentrated to give N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-{[3′-formyl-6-(methyloxy)-3-biphenylyl]methyl}-5-methyl-1,3-benzenedicarboxamide (632 mg, 0.873 mmol, 64.3% yield) as a white solid. LC-MS m/z 689.8 (M+H)+, 0.95 min (ret time); mp 117-119° C.

1. customThe vials were capped
2. customthe mixtures were microwaved at normal power in the Emrys Optimizer at 100° C. for 15 min
3. customwas partitioned between EtOAc (75 mL) and water (20 mL)
4. customThe phases were separated
5. washthe organic phase was washed with water (2×20 mL), brine (20 mL)
6. dry with materialdried over anhydrous Na2SO4
7. filtrationfiltered
8. customevaporated
9. customto give the crude residue
10. customabsorbed on Isolute® Sorbent
11. custompurified by CombiFlash
12. washeluted with 0-10% MeOH/DCM
13. concentrationconcentrated