Sodium cyanoborohydride → 2-(6-(4-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoroindolin-1-yl)ethanol

HRID 331025Notes

Reaction equation

HRID 331025 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH3:24])[CH:9]=[C:10]([C:11]3[CH:19]=[C:18]4[C:14]([CH:15]=[CH:16][N:17]4[CH2:20][CH2:21][OH:22])=[CH:13][C:12]=3[F:23])[C:3]=12.C([BH3-])#N.[Na+]>C(O)(=O)C>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH3:24])[CH:9]=[C:10]([C:11]3[CH:19]=[C:18]4[C:14]([CH2:15][CH2:16][N:17]4[CH2:20][CH2:21][OH:22])=[CH:13][C:12]=3[F:23])[C:3]=12

Participants

4

Reactant 2

HCID 5003444Sodium cyanoborohydrideHCID 867202882-(6-(4-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-1H-indol-1-yl)ethanol

Product 1

HCID 867202892-(6-(4-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoroindolin-1-yl)ethanolYield 78.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 2-(6-(4-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-1H-indol-1-yl)ethanol (D40) (780 mg, 2.009 mmol) in 5 mL of acetic acid cooled in an ice bath was added sodium cyanoborohydride (189 mg, 3.01 mmol). The ice bath was removed and the reaction mixture was left to stir at RT for 1 hour. The reaction mixture was once again cooled in an ice bath then quenched and basified by the slow addition of 2N sodium carbonate aqueous solution. The aqueous layer was extracted with DCM (3×50 mL), the organic layers were combined, passed through a hydrophobic frit and concentrated. The crude was purified by column chromatography on silica gel, eluting with a gradient of 0-50% ethyl acetate in cyclohexane to afford the title compound (614 mg). LCMS (A): m/z (M+H)+390/392, C18H17BrFN3O requires 389/391 (acidic).

Workup

  1. customThe ice bath was removed
  2. waitthe reaction mixture was left
  3. temperatureThe reaction mixture was once again cooled in an ice bath
  4. customthen quenched
  5. additionbasified by the slow addition of 2N sodium carbonate aqueous solution
  6. extractionThe aqueous layer was extracted with DCM (3×50 mL)
  7. concentrationconcentrated
  8. customThe crude was purified by column chromatography on silica gel
  9. washeluting with a gradient of 0-50% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-69ff283ca4a344f7a2c4dfc3a0864156
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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