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

HRID 1774972Notes

Reaction equation

HRID 1774972 reaction equation
[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

Participants

9

Reactant 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

Product 1

HCID 866766845-bromo-3-phenyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridineYield 82.6%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

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]

Workup

  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)

Sources & evidence

ORD record
ord-b1d32638ab044289bcbbde84e8a8596e
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

Loading…