Potassium Carbonate → HCID 67045860, Verbindung

HRID 2203972Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2203972
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-891d03c2385e474abf0373c43f7570af
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09365568B2

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