Sodium Bicarbonate → HCID 178508702, Verbindung

HRID 1909915Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1909915
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11](=[O:19])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:6][CH2:5]2.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:44]1[C:52]2[C:47](=[N:48][CH:49]=[N:50][C:51]=2[NH2:53])[NH:46][N:45]=1.C([O-])(O)=O.[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O1CCOCC1>[C:13]1([CH2:12][C:11]([N:7]2[C:8]3[C:4](=[CH:3][C:2]([C:44]4[C:52]5[C:47](=[N:48][CH:49]=[N:50][C:51]=5[NH2:53])[NH:46][N:45]=4)=[CH:10][CH:9]=3)[CH2:5][CH2:6]2)=[O:19])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Komponenten

8

Edukt 5

HCID 516892Sodium BicarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 668241055-bromo-1-(phenylacetyl)-2,3-dihydro-1H-indoleHCID 178508701HCID 178508701, Verbindung

Produkt 1

HCID 178508702HCID 178508702, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418807HCID 178418807, VerbindungKatalysator2×HCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a mixture of 5-bromo-1-(phenylacetyl)-2,3-dihydro-1H-indole (148 mg, 0.467 mmol),bis(pinacolato)diboron (125 mg, 0.491 mmol), and potassium acetate (138 mg, 1.402 mmol) was added 1,4-dioxane (6 mL), and the mixture was degassed with N2 for 10 minutes. PdCl2(dppf)-CH2Cl2 adduct (19.08 mg, 0.023 mmol) was added, and the reaction mixture was stirred for 3 hours at 100 C into a sealed vessel. The reaction was cooled down to room temperature. 3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (100 mg, 0.467 mmol) and sat. aq. NaHCO3 (2 mL) were added, and N2 gas was bubbled through the mixture for 10 minutes. PdCl2(dppf)-CH2Cl2 adduct (19.08 mg, 0.023 mmol) was added, the vessel was sealed, and the reaction mixture was stirred for 3 days at 100 C. The mixture was allowed to cool to room temperature and poured onto water (˜150 mL). The resulting mixture was filtered, and the resulting solid was triturated with EtOAc. To the dark solid in the filter was added a 80:20 mixture of CHCl3:CH3OH (˜7 mL), and the resulting mixture was filtered. The filtrate was injected into a 90 g SiO2 columns. Flash chromatography on SiO2 (gradient: 100% CHCl3 to 90:10:1 CHCl3:CH3OH:NH4OH) provided the title compound. Trituration with Et2O afforded the title compound 3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (35 mg) as a grey solid. 1H NMR (400 MHz, DMSO-d6) 3.24 (t, J=8.34 Hz, 2H), 3.89 (s, 2H), 4.24 (t, J=8.46 Hz, 2H), 7.22-7.40 (m, 6H), 7.44 (d, J=8.34 Hz, 1H), 7.50 (s, 1H), 8.17-8.23 (m, 2H), 13.51 (s, 1H)

Aufarbeitung

  1. customthe mixture was degassed with N2 for 10 minutes
  2. customN2 gas was bubbled through the mixture for 10 minutes
  3. customthe vessel was sealed
  4. stirringthe reaction mixture was stirred for 3 days at 100 C
  5. temperatureto cool to room temperature
  6. additionpoured onto water (˜150 mL)
  7. filtrationThe resulting mixture was filtered
  8. customthe resulting solid was triturated with EtOAc
  9. additionTo the dark solid in the filter was added
  10. additiona 80:20 mixture of CHCl3
  11. filtrationCH3OH (˜7 mL), and the resulting mixture was filtered

Quellen und Nachweise

ORD-Eintrag
ord-0f1a30919d5a4622889aefebf50df670
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08598156B2

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