Dichloromethane → 5-bromo-3-phenyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

HRID 1774972Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1774972
[Br:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[N:9][N:8]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[C:5]2=[CH:6][N:7]=1.[C:18]1(B(O)O)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+].C([O-])(=O)C.[K+]>C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl.C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[N:9][N:8]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[C:5]2=[CH:6][N:7]=1

Komponenten

9

Edukt 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 517044Potassium AcetateHCID 726984825-bromo-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

Produkt 1

HCID 866766845-bromo-3-phenyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridineAusbeute 82,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24290Palladium ChlorideKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

In an oven-dried flask was placed 5-bromo-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine (2.0 g, 4.90 mmol), phenylboronic acid (627.5 mg, 5.15 mmol), and bis(diphenylphosphino)ferrocene]dichloropalladium (II), complexed with dichloromethane (1:1) (200.14 mg, 0.24 mmol). Degassed acetonitrile (53 mL) was added, followed by 1.0 M aqueous sodium carbonate solution (7.4 mL) and 1.0 M aqueous potassium acetate solution (7.4 mL). The reaction mixture was degassed under N2 for 5 minutes more and stirred at 80° C. under N2 for 1 h. The reaction mixture was cooled to room temperature, partitioned between EtOAc and water and the layers were separated. The organic layer was washed with water (3×) and brine, dried over Na2SO4 and concentrated to an oil. The crude product was purified using flash column chromatography (Si-PPC gradient elution, solvent: 0-60% ethyl acetate in heptanes) to give 5-bromo-3-phenyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine as a solid (1.45 g, 82.47%). 1H NMR (400 MHz, CDCl3) δ 8.95 (d, J=0.9 Hz, 1H), 8.08 (d, J=0.9 Hz, 1H), 7.94-7.88 (m, 2H), 7.55-7.48 (m, 2H), 7.48-7.41 (m, 1H), 5.86 (dd, J=8.6, 2.6 Hz, 1H), 4.07-3.97 (m, 1H), 3.80 (ddd, J=12.3, 8.9, 3.8 Hz, 1H), 2.54 (qd, J=9.0, 5.5 Hz, 1H), 2.24-2.11 (m, 2H), 1.89-1.67 (m, 3H). LC/MS: m/z 274.1 (des-THP) [M+1]

Aufarbeitung

  1. customIn an oven-dried flask was placed
  2. customThe reaction mixture was degassed under N2 for 5 minutes more
  3. temperatureThe reaction mixture was cooled to room temperature
  4. custompartitioned between EtOAc and water
  5. customthe layers were separated
  6. washThe organic layer was washed with water (3×) and brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to an oil
  9. customThe crude product was purified
  10. washflash column chromatography (Si-PPC gradient elution, solvent: 0-60% ethyl acetate in heptanes)

Quellen und Nachweise

ORD-Eintrag
ord-b1d32638ab044289bcbbde84e8a8596e
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09260425B2

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