Реакция #744611

Уравнение реакции

AcOH

TFA

N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(3′-formyl-3-biphenylyl)methyl]propanediamide

1,1-dimethylethyl (2R)-2-methyl-1-piperazinecarboxylate

NaB(OAc)3H

→

title compound

Выход 9.9%

N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(3′-{[(3R)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]propanediamide

Выход 9.9%

Растворители

dimethyl sulfoxide

dichloromethane

Условия реакции

Обработка

1. 1
   ДругоеThe reaction was quenched with saturated NaHCO3
2. 2
   Экстракцияextracted with EtOAc (3×1 mL)
3. 3
   ПромывкаCombined organic layers were washed with saturated NaCl
4. 4
   Сушкаdried (Na2SO4)
5. 5
   Концентрированиеconcentrated
6. 6
   workup.DISSOLUTIONThe crude products were redissolved in MeOH/DMSO (1/1)
7. 7
   Другоеpurified
8. 8
   Другоеsolvent evaporated
9. 9
   Другоеa GeneVac EZ-2 evaporator
10. 10
    Другоеthat mixture was placed in a Glas-Col evaporator overnight
11. 11
    workup.DISSOLUTIONthe residue was redissolved in MeOH/DMSO
12. 12
    Другоеpurified
13. 13
    Другоеsolvent was evaporated
14. 14
    Другоеa GeneVac EZ-2 evaporator That residue

Методика

To N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(3′-formyl-3-biphenylyl)methyl]propanediamide (50 mg, 0.086 mmol) was added 1,1-dimethylethyl (2R)-2-methyl-1-piperazinecarboxylate (34.4 mg, 0.172 mmol) followed by NaB(OAc)3H (36.4 mg, 0.172 mmol) and AcOH (4.91 μL, 0.086 mmol) in dimethyl sulfoxide (DMSO) (0.5 mL). The mixture was stirred overnight at room temperature. The reaction was quenched with saturated NaHCO3 and extracted with EtOAc (3×1 mL). Combined organic layers were washed with saturated NaCl, dried (Na2SO4) and concentrated. The crude products were redissolved in MeOH/DMSO (1/1) and purified using a Gilson HPLC (acidic condition). Product fractions were combined and solvent evaporated using a GeneVac EZ-2 evaporator. To the obtained residue was added TFA (0.198 mL, 2.57 mmol) in dichloromethane (0.2 mL) and that mixture was placed in a Glas-Col evaporator overnight and then the residue was redissolved in MeOH/DMSO and purified using a Gilson HPLC (acidic condition). Product fractions were combined and solvent was evaporated using a GeneVac EZ-2 evaporator That residue was basified by cartridge to afford the title compound 5.7 mg (9.4%). LC-MS m/z 667 (M+H)+.

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