Methanol → 6-((1R,2S)-2-Aminocyclohexylamino)-4-(3-(methylsulfonyl)phenylamino)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

HRID 516017Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 516017
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[CH:18]=[C:17]([C:19]#[N:20])[C:12](C(OC)=O)=[C:11]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:23]=2)[N:10]=1.[CH3:32][OH:33]>[Pd].Cl>[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[N:10]=[C:11]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:23]=2)[C:12]2[C:32](=[O:33])[NH:20][CH2:19][C:17]=2[CH:18]=1

Komponenten

5

Edukt 2

HCID 887MethanolHCID 67237982Methyl 6-((1R,2S)-2-aminocyclohexylamino)-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate

Produkt 1

HCID 532524386-((1R,2S)-2-Aminocyclohexylamino)-4-(3-(methylsulfonyl)phenylamino)-1H-pyrrolo[3,4-c]pyridin-3(2H)-oneAusbeute 34 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23938PalladiumKatalysatorHCID 313Hydrochloric AcidLösungsmittel

Versuchsvorschrift

A mixture of methyl 6-((1R,2S)-2-aminocyclohexylamino)-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate (117.3 mg, 0.264 mmol) and palladium on carbon (23.6 mg, 0.222 mmol) in MeOH (4 mL) and 1N HCl (4 mL) was stirred at RT for 16 h under a hydrogen atmosphere. The mixture was filtered to remove the catalyst and the filtrate was treated with saturated aq NaHCO3 (20 mL) and stirred at RT for 20 h. The mixture was concentrated under reduced pressure and the residue was extracted with EtOAc/THF (2/1, 2×30 mL). The organic layers were washed with saturated aq NaHCO3 (15 mL), water (15 mL) and brine (15 mL), were dried over anhydrous Na2SO4, and then filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (DM1020, EtOAc/MeOH=20/1) to give the desired product (37.2 mg, 34%). The product was recrystallized from EtOH to give the title compound as a colorless solid (13.2 mg, 12%). 1H-NMR (DMSO-d6) δ ppm 1.31-1.41 (m, 4H), 1.55-1.68 (m, 6H), 3.05 (s, 1H), 3.21 (s, 3H), 4.08 (s, 1H), 4.23 (s, 2H), 6.17 (s, 1H), 6.78-6.79 (m, 1H), 7.46-7.47 (m, 1H), 7.53-7.56 (m, 1H), 7.96-7.99 (m, 2H), 8.49 (s, 1H), 9.18 (s, 1H).

Aufarbeitung

  1. filtrationThe mixture was filtered
  2. customto remove the catalyst
  3. additionthe filtrate was treated with saturated aq NaHCO3 (20 mL)
  4. stirringstirred at RT for 20 h
  5. concentrationThe mixture was concentrated under reduced pressure
  6. extractionthe residue was extracted with EtOAc/THF (2/1, 2×30 mL)
  7. washThe organic layers were washed with saturated aq NaHCO3 (15 mL), water (15 mL) and brine (15 mL)
  8. dry with materialwere dried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe residue was purified by column chromatography (DM1020, EtOAc/MeOH=20/1)

Quellen und Nachweise

ORD-Eintrag
ord-3091201c98654ecc99b8dfa3c053d8c1
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108970B2

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