反应详情

A mixture of 2-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]hexanoic acid, 1,1-dimethylethyl (2S)-4-{[5′-(aminomethyl)-2′-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate (424 mg, 0.98 mmol), HBTU (535 mg, 1.41 mmol) and Et3N (0.82 mL, 5.89 mmol) in DCM (3 mL) was stirred at room temperature overnight. The reaction was quenched with saturated NaHCO3 and extracted with DCM twice. The combined organic layers were then washed with water followed by a brine wash. The organic layer was then concentrated under vacuum to give a crude residue: LC-MS m/z 841 (M+H)+. The crude residue was dissolved in 25% TFA in DCM (2 mL) and stirred at RT for 2 h. It was purified with a Gilson HPLC (with 0.1% TFA condition) eluting with 10 to 70% CH3CN in water at a flowrate of 20 mL/min. The fractions were combined and then converted to the free base with saturated NaHCO3. The organic layer was dried over sodium sulfate, filtered and then concentrated to give 2-butyl-N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(6-fluoro-3′-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]propanediamide as a solid (59 mg, 12%). LC-MS m/z 741 (M+H)+.

1. customThe reaction was quenched with saturated NaHCO3
2. extractionextracted with DCM twice
3. washThe combined organic layers were then washed with water
4. washwash
5. concentrationThe organic layer was then concentrated under vacuum
6. customto give a crude residue
7. stirringstirred at RT for 2 h
8. customIt was purified with a Gilson HPLC (with 0.1% TFA condition)
9. washeluting with 10 to 70% CH3CN in water at a flowrate of 20 mL/min
10. dry with materialThe organic layer was dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated