Reaktion #651812

Reaktionsgleichung

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

Lösungsmittel

1,2-dichloroethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas placed on an oscillating shaker overnight at room temperature
2. 2
   SonstigeThe reaction was quenched with sat. aq. NaHCO3
3. 3
   Extraktionextracted with 1,2-dichloroethane (2×)
4. 4
   WaschenCombined organic extracts were washed with sat. aq. NaCl
5. 5
   Trocknendried (Na2SO4)
6. 6
   Einengenconcentrated to a residue
7. 7
   workup.ADDITIONcontaining 25% TFA
8. 8
   Sonstigethe reaction
9. 9
   SonstigePurification
10. 10
    workup.ADDITIONFractions containing the clean desired product
11. 11
    workup.ADDITIONdiluted with EtOAc
12. 12
    Waschenwashed with sat. aq. NaHCO3
13. 13
    Extraktionand the aq. phase was back-extracted with EtOAc
14. 14
    WaschenCombined organic extracts were washed with sat. aq. NaCl
15. 15
    Trocknendried (Na2SO4)
16. 16
    Einengenconcentrated to a residue

Vorschrift

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)+.

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