Methyl iodide → 4-bromo-3-(5-fluoro-1-(2-methoxyethyl)indolin-6-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine

HRID 331026Notes

Reaction equation

HRID 331026 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]([CH2:15][CH2:16][N:17]4[CH2:20][CH2:21][OH:22])=[CH:13][C:12]=3[F:23])[C:3]=12.[OH-].[K+].[CH3:27]I>CS(C)=O>[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][O:22][CH3:27])=[CH:13][C:12]=3[F:23])[C:3]=12

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 14797Potassium HydroxideHCID 867202892-(6-(4-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoroindolin-1-yl)ethanol

Product 1

HCID 867202904-bromo-3-(5-fluoro-1-(2-methoxyethyl)indolin-6-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridineYield 68.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 2-(6-(4-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoroindolin-1-yl)ethanol (D41) (150 mg, 0.384 mmol) in DMSO (3 mL) was added potassium hydroxide (64.7 mg, 1.153 mmol) followed by methyl iodide (0.036 mL, 0.577 mmol). The reaction mixture was stirred at RT for 1 hour, after which an additional 0.5 eq of methyl iodide (0.012 mL) was added. The reaction mixture was stirred for an additional hour. The reaction mixture was quenched by the addition of saturated ammonium chloride aqueous solution (20 mL). The aqueous layer was extracted with DCM (3×40 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 0-40% ethyl acetate in cyclohexane to afford title compound (106 mg). LCMS (A): m/z (M+H)+ 404/406, C19H19BrFN3O requires 403/405 (acidic).

Workup

  1. stirringThe reaction mixture was stirred for an additional hour
  2. customThe reaction mixture was quenched by the addition of saturated ammonium chloride aqueous solution (20 mL)
  3. extractionThe aqueous layer was extracted with DCM (3×40 mL)
  4. concentrationconcentrated
  5. customThe crude was purified by column chromatography on silica gel
  6. washeluting with a gradient of 0-40% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-b3a53dc4d6ca4375a59efcadcd84d085
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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