Реакция #651812

Уравнение реакции

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

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

sodium triacetoxyborohydride

AcOH

→

title compound

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

Растворители

1,2-dichloroethane

Условия реакции

Обработка

1. 1
   Другоеwas placed on an oscillating shaker overnight at room temperature
2. 2
   ДругоеThe reaction was quenched with sat. aq. NaHCO3
3. 3
   Экстракцияextracted with 1,2-dichloroethane (2×)
4. 4
   ПромывкаCombined organic extracts were washed with sat. aq. NaCl
5. 5
   Сушкаdried (Na2SO4)
6. 6
   Концентрированиеconcentrated to a residue
7. 7
   workup.ADDITIONcontaining 25% TFA
8. 8
   Другоеthe reaction
9. 9
   ДругоеPurification
10. 10
    workup.ADDITIONFractions containing the clean desired product
11. 11
    workup.ADDITIONdiluted with EtOAc
12. 12
    Промывкаwashed with sat. aq. NaHCO3
13. 13
    Экстракцияand the aq. phase was back-extracted with EtOAc
14. 14
    ПромывкаCombined organic extracts were washed with sat. aq. NaCl
15. 15
    Сушкаdried (Na2SO4)
16. 16
    Концентрированиеconcentrated to a residue

Методика

A mixture of N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(6-fluoro-3′-formyl-3-biphenylyl)methyl]-1,3-benzenedicarboxamide (100 mg, 0.000152 mol) in 1,2-dichloroethane (4 mL) with 1,1-dimethylethyl (2R)-2-methyl-1-piperazinecarboxylate (48 mg, 0.00024 mol) and sodium triacetoxyborohydride (68 mg, 0.00032 mol) and AcOH (12 μL) was placed on an oscillating shaker overnight at room temperature. The reaction was quenched with sat. aq. NaHCO3, then extracted with 1,2-dichloroethane (2×). Combined organic extracts were washed with sat. aq. NaCl and dried (Na2SO4) and concentrated to a residue. The crude product was taken up in 1,2-dichloroethane (10 mL) containing 25% TFA and allowed to stand at room temperature for 1.5 h. LC-MS showed the reaction to be complete and the solution stripped to dryness. Purification was carried out on Gilson HPLC instrument with acetonitrile-water (0.1% TFA) gradient; C18-RP Column. Fractions containing the clean desired product were combined; diluted with EtOAc; washed with sat. aq. NaHCO3; and the aq. phase was back-extracted with EtOAc. Combined organic extracts were washed with sat. aq. NaCl and dried (Na2SO4) and concentrated to a residue. It was taken up in a small amount of 1,2-dichloroethane and transferred to a vial and pumped down to afford the title compound as an ivory colored solid [62.1 mg (53%)]. LC-MS m/z 747.3 (M+H)+.

Источник