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Acetic Acid → N-({3'-[(1S,4S)-2,5-Diazabicyclo [2.2.1]hept-2-ylmethyl]-2-methyl-3-biphenylyl}methyl)-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide

HRID 564624
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 564624
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:48][CH3:49])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[C:34]([CH3:47])=[C:35]([C:39]5[CH:44]=[CH:43][CH:42]=[C:41](C=O)[CH:40]=5)[CH:36]=[CH:37][CH:38]=4)=[O:30])[CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[N:50]1([C:56](OC(C)(C)C)=O)[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]1.[C:63](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CC(O)=O>ClCCCl>[C@H:55]12[CH2:63][C@H:52]([NH:53][CH2:54]1)[CH2:51][N:50]2[CH2:56][C:41]1[CH:40]=[C:39]([C:35]2[CH:36]=[CH:37][CH:38]=[C:33]([CH2:32][NH:31][C:29]([C:25]3[CH:26]=[CH:27][CH:28]=[C:23]([C:21]([NH:20][CH2:19][C:10]4[C:11]([NH:12][CH:13]5[CH2:14][CH2:15][O:16][CH2:17][CH2:18]5)=[C:6]5[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[C:7]5=[N:8][C:9]=4[CH2:48][CH3:49])=[O:22])[CH:24]=3)=[O:30])[C:34]=2[CH3:47])[CH:44]=[CH:43][CH:42]=1
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 57813263HCID 57813263, Verbindung

Produkt 1

HCID 57813443N-({3'-[(1S,4S)-2,5-Diazabicyclo [2.2.1]hept-2-ylmethyl]-2-methyl-3-biphenylyl}methyl)-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide
Ausbeute 19 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 111,2-DichloroethaneLösungsmittel

Versuchsvorschrift

A mixture of N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(3′-formyl-2-methyl-3-biphenylyl)methyl]-1,3-benzenedicarboxamide (100 mg, 0.000152 mol) in 1,2-dichloroethane (4 mL), 1,1-dimethylethyl 1-piperazinecarboxylate (44.6 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 3 h. LC-MS showed the reaction to be complete. Solvent was stripped off. Purification was carried out on a 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 a beige colored solid [21.4 mg (19%)]. LC-MS m/z 741.7 (M+H)+.

Aufarbeitung

  1. customwas placed on an oscillating shaker overnight at room temperature
  2. customThe reaction was quenched with sat. aq. NaHCO3
  3. extractionextracted with 1,2-dichloroethane (2×)
  4. washCombined organic extracts were washed with sat. aq. NaCl
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated to a residue
  7. additioncontaining 25% TFA
  8. customthe reaction
  9. customPurification
  10. additionFractions containing the clean desired product
  11. additiondiluted with EtOAc
  12. washwashed with sat. aq. NaHCO3
  13. extractionand the aq. phase was back-extracted with EtOAc
  14. washCombined organic extracts were washed with sat. aq. NaCl
  15. dry with materialdried (Na2SO4)
  16. concentrationconcentrated to a residue

Quellen und Nachweise

ORD-Eintrag
ord-749c9075bee94902889c92efd9662256
Quelldatensatz
uspto-grants-2011_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08067408B2

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