Sodium Carbonate → 2-(5-(2-(Aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)ethanol

HRID 1666769Notes

Reaction equation

HRID 1666769 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH2:20][CH2:21][OH:22])[N:15]=[CH:14]3)=[C:6]([CH:9]=1)[C:7]#[N:8].[BH4-].[Na+].C([O-])([O-])=O.[Na+].[Na+]>CO>[NH2:8][CH2:7][C:6]1[CH:9]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH2:20][CH2:21][OH:22])[N:15]=[CH:14]2

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 4311764Sodium borohydrideHCID 445421215-fluoro-2-(1-(2-hydroxyethyl)-1H-indazol-5-yloxy)benzonitrile

Product 1

HCID 445421222-(5-(2-(Aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)ethanol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (5-fluoro-2-(1-(2-hydroxyethyl)-1H-indazol-5-yloxy)benzonitrile (1.0 g, 3.36 mmol) and NCl2.6H2O (148 mg, 0.336 mmol) in MeOH (30 mL) was added NaBH4 (636 mg, 16.8 mmol) in portions (2-3), and the reaction was stirred for 3 hours. A solution of saturated Na2CO3 (15 mL) was slowly added and the mixture was stirred for 75 minutes, during which a fine solid formed. The reaction mixture was filtered thru GF/F and the cake was washed with MeOH (20 mL). The filtrate was concentrated to about 15 mL under vacuum, isopropyl acetate (20 mL) was added, and the mixture was concentrated. To the concentrate was added isopropyl acetate (20 mL) and the mixture was stirred for 5 minutes. The phases were separated, and the organic layer was washed with 10% brine (20 mL). Citric acid (0.1 M, 20 mL) was added and the phases were vigorously mixed. The organic layer was removed and the aqueous was washed with isopropyl acetate (20 mL) and EtOAc (20 mL). To the aqueous layer was added isopropyl acetate (20 mL) and 50% NaOH (1 mL) was added. The phases were vigorously mixed and the aqueous was removed. The organic was washed with 10% brine (20 mL), dried over Na2SO4 and concentrated to 850 mg (85%).

Workup

  1. stirringthe mixture was stirred for 75 minutes, during which a fine solid
  2. customformed
  3. filtrationThe reaction mixture was filtered
  4. washwas washed with MeOH (20 mL)
  5. concentrationThe filtrate was concentrated to about 15 mL under vacuum, isopropyl acetate (20 mL)
  6. additionwas added
  7. concentrationthe mixture was concentrated
  8. additionTo the concentrate was added isopropyl acetate (20 mL)
  9. stirringthe mixture was stirred for 5 minutes
  10. customThe phases were separated
  11. washthe organic layer was washed with 10% brine (20 mL)
  12. additionCitric acid (0.1 M, 20 mL) was added
  13. additionthe phases were vigorously mixed
  14. customThe organic layer was removed
  15. washthe aqueous was washed with isopropyl acetate (20 mL) and EtOAc (20 mL)
  16. additionTo the aqueous layer was added isopropyl acetate (20 mL) and 50% NaOH (1 mL)
  17. additionwas added
  18. additionThe phases were vigorously mixed
  19. customthe aqueous was removed
  20. washThe organic was washed with 10% brine (20 mL)
  21. dry with materialdried over Na2SO4
  22. concentrationconcentrated to 850 mg (85%)

Sources & evidence

ORD record
ord-014f6fdd6e5a483c8e1c41af5c9b4f59
Source dataset
uspto-grants-2011_10
Patent number
US08044083B2

Reaction notes

Loading…