Methanol → {3-[(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-hydroxy-methyl]-2,4-difluoro-phenyl}-carbamic acid methyl ester

HRID 60081Notes

Reaction equation

HRID 60081 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:11][O:12][C:13](=[O:25])[NH:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]([CH:22]=[O:23])[C:16]=1[F:24].CO.[OH-].[K+]>O>[CH3:11][O:12][C:13](=[O:25])[NH:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]([CH:22]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=3)[NH:8][CH:9]=2)[OH:23])[C:16]=1[F:24]

Participants

6

Reactant 4

HCID 887MethanolHCID 14797Potassium HydroxideHCID 103079325-bromo-1H-pyrrolo[2,3-b]pyridineHCID 58368834(2,4-Difluoro-3-formyl-phenyl)-carbamic acid methyl ester

Product 1

HCID 58368953{3-[(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-hydroxy-methyl]-2,4-difluoro-phenyl}-carbamic acid methyl esterYield 91.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Into a reaction flask under nitrogen, 5-bromo-1H-pyrrolo[2,3-b]pyridine (4, 1.00 g, 5.08 mmol) is combined with (2,4-difluoro-3-formyl-phenyl)-carbamic acid methyl ester (3, 1.09 g, 5.08 mmol), 10 mL of methanol and potassium hydroxide (0.41 g, 7.31 mmol). The reaction is stirred at room temperature overnight, then diluted with 30 mL of water and extracted with 1×50 mL, then 2×30 mL of ethyl acetate. The organic layers are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with a gradient of ethyl acetate:hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (5, 1.91 g, 91%).

Workup

  1. extractionextracted with 1×50 mL
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated under vacuum
  5. customThe resulting material is purified by silica gel column chromatography
  6. washeluting with a gradient of ethyl acetate
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-330b30895f254e13b1624ed59cbcd54f
Source dataset
uspto-grants-2016_09
Patent number
US09440969B2

Reaction notes

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