反应详情

温度

150 °C

237(a) A mixture of N-{[3-bromo-5-(methyloxy)phenyl]methyl}-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide (150 mg, 0.23 mmol), {3-[((3S)-4-{[(1,1-dimethylethyl)oxy]carbonyl}-3-methyl-1-piperazinyl)methyl]phenyl}boronic acid (100 mg, 0.30 mmol), Na2CO3 (74 mg, 0.69 mmol), Pd(PPh3)4 (13.3 mg, 0.01 mmol), water (0.75 mL) in dioxane (2.25 mL) was degassed for 5 min. and then heated in a microwave for 30 min at 150° C. The reaction was quenched with water and then extracted with ethyl acetate twice. The combined organic layers were washed with water and brine. The organic layer was filtered though a 0.45 μM filter and then concentrated to give a crude residue. It was then purified using Combi Flash chromatography, eluting with 0 to 10% MeOH in DCM. The product fractions were combined and concentrated under vacuum to give 1,1-dimethylethyl (2S)-4-{[3′-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]phenyl}carbonyl)amino]methyl}-5′-(methyloxy)-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate as a solid (130 mg, 65%): LC-MS m/z 859 (M+H)+.

1. customwas degassed for 5 min.
2. customThe reaction was quenched with water
3. extractionextracted with ethyl acetate twice
4. washThe combined organic layers were washed with water and brine
5. filtrationThe organic layer was filtered though a 0.45 μM
6. filtrationfilter
7. concentrationconcentrated
8. customto give a crude residue
9. customIt was then purified
10. washeluting with 0 to 10% MeOH in DCM
11. concentrationconcentrated under vacuum