Ammonia → HCID 178505544, compound

HRID 2376747Notes

Reaction equation

HRID 2376747 reaction equation
N[C:2]1[C:10]2[C:5](=[N:6][C:7]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[C:8]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)[CH:9]=2)[NH:4][N:3]=1.N([O-])=O.[Na+].C(=O)(O)[O-].[Na+].N.[BrH:34]>O>[Br:34][C:2]1[C:10]2[C:5](=[N:6][C:7]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[C:8]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)[CH:9]=2)[NH:4][N:3]=1

Participants

7

Reactant 5

HCID 222AmmoniaHCID 260Hydrogen Bromide2×HCID 516892Sodium BicarbonateHCID 23668193Sodium NitriteHCID 178509219HCID 178509219, compound

Product 1

HCID 178505544HCID 178505544, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
2.5 °C

Procedure

To a solution of 3-amino-6-(4-fluorophenyl)-5-(4-pyridyl)-1H-pyrazolo[3,4-b]pyridine (0.20 g, 0.7 mmol, obtained in example 70) in 48% HBr (1 mL) at 0° C., a solution of NaNO2 (0.05 g, 0.7 mmol) in water (0.1 mL) was added dropwise over a period of 15 minutes maintaining the temperature at 0-5° C. The mixture was stirred for 15 min at this temperature. Then, a solution of CuBr (0.24 g, 1.7 mmol) in 48% HBr (1 mL) was added slowly at 0° C. The resulting solution was stirred for 3 h at 0° C. It was allowed to reach room temperature, neutralized at pH=7 with saturated sodium bicarbonate and a 30% aqueous NH3. It was filtered and the solid was washed with a mixture of CH2Cl2 and water. The organic phase was washed with 1 N NaOH and the aqueous phase extracted with EtOAc. The combined organic phases were dried over Na2SO4 and concentrated to dryness. The crude product obtained was purified by chromatography on silica gel using CHCl3-MeOH mixtures of increasing polarity as eluent, to afford 50 mg of the title compound (yield: 21%).

Workup

  1. stirringThe resulting solution was stirred for 3 h at 0° C
  2. customto reach room temperature
  3. filtrationIt was filtered
  4. washthe solid was washed with a mixture of CH2Cl2 and water
  5. washThe organic phase was washed with 1 N NaOH
  6. extractionthe aqueous phase extracted with EtOAc
  7. dry with materialThe combined organic phases were dried over Na2SO4
  8. concentrationconcentrated to dryness
  9. customThe crude product obtained
  10. customwas purified by chromatography on silica gel
  11. temperatureof increasing polarity as eluent

Sources & evidence

ORD record
ord-1aaef72c3dcd40399d73b70f8e04e5c2
Source dataset
uspto-grants-2008_12
Patent number
US07468376B2

Reaction notes

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