Potassium Carbonate → HCID 67045860, Verbindung

HRID 408404Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 408404
Br[C:2]1[C:3]([N:24]2[CH2:29][CH2:28][CH2:27][C@@H:26]([NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:25]2)=[C:4]2[C:10]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])=[CH:9][N:8]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:5]2=[N:6][CH:7]=1.[C:38](=O)([O-])[O-].[K+].[K+].CB1OB(C)OB(C)O1.CC#N.O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:34]([O:33][C:31]([NH:30][C@@H:26]1[CH2:27][CH2:28][CH2:29][N:24]([C:3]2[C:2]([CH3:38])=[CH:7][N:6]=[C:5]3[N:8]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH:9]=[C:10]([NH:11][C:12]([CH:14]4[CH2:16][CH2:15]4)=[O:13])[C:4]=23)[CH2:25]1)=[O:32])([CH3:36])([CH3:37])[CH3:35]

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 18373917Acetonitrile--water (1/1)HCID 67045247HCID 67045247, Verbindung

Produkt 1

HCID 67045860HCID 67045860, VerbindungAusbeute 55,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A solution of (R)-tert-butyl 5-bromo-4-(3-(tert-butoxycarbonylamino) piperidin-1-yl)-3-(cyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (175 mg, 0.303 mmol) in dioxane (5 mL) at room temperature was treated with potassium carbonate (107 mg, 0.771 mmol), Pd(PPh3)4 (31.5 mg, 0.0272 mmol), and 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (34.2 mg, 0.272 mmol). N2 was bubbled through the mixture for 5 minutes, and the mixture was heated at reflux for 24 hours under N2 atmosphere. The mixture was then diluted with EtOAc (20 mL) and washed with water (1×5 mL). The organic layer was separated, dried (MgSO4), filtered, and concentrated in vacuo. The residue obtained was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 40-95% CH3CN/water, 24 CV) to provide (R)-tert-butyl 4-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-3-(cyclopropanecarboxamido)-5-methyl-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (86 mg, 55% yield) as a solid. LCMS (APCI+) m/z 514.1 (M+H)+.

Aufarbeitung

  1. customN2 was bubbled through the mixture for 5 minutes
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 24 hours under N2 atmosphere
  4. additionThe mixture was then diluted with EtOAc (20 mL)
  5. washwashed with water (1×5 mL)
  6. customThe organic layer was separated
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue obtained
  11. customwas purified by reverse phase chromatography (Biotage SP4

Quellen und Nachweise

ORD-Eintrag
ord-4ebfee1fab9b4bc2bace098ec39465d1
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08758830B2

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