反应详情

N-[(3-Bromo-4-methylphenyl)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 (840 mg, 1.297 mmol), (3-formylphenyl)boronic acid (194 mg, 1.297 mmol), potassium carbonate (538 mg, 3.89 mmol), and Pd(Ph3P)4 (74.9 mg, 0.065 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 mixture was 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 washed with water (2×20 mL), brine (20 mL), dried over anhydrous Na2SO4 filtered and evaporated to give the crude residue. The residue was taken up in DCM and absorbed on Isolute® Sorbent and purified by Combiflash using an 80 g silica column eluted with 0-10% DCM/MeOH. 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-methyl-3-biphenylyl)methyl]-5-methyl-1,3-benzenedicarboxamide (537 mg, 0.789 mmol, 60.8% yield)) as a white solid. LC-MS m/z 673.4 (M+H)+, 0.99 min (ret time); mp 117-120° C.

1. customThe vials were capped
2. customthe mixture was 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 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% DCM/MeOH
13. concentrationconcentrated