(1-Bromoethyl)benzene → methyl 2-methyl-1-(1-phenylethyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate

HRID 2206501Notes

Reaction equation

HRID 2206501 reaction equation
[CH3:1][C:2]1[NH:10][C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[C:11]([O:13][CH3:14])=[O:12].[H-].[Na+].Br[CH:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH3:19].[Cl-].[NH4+]>CN(C)C=O>[CH3:1][C:2]1[N:10]([CH:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH3:19])[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[C:11]([O:13][CH3:14])=[O:12]

Participants

6

Reactant 4

HCID 11454(1-Bromoethyl)benzeneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 89740922Methyl 2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylate

Product 1

HCID 89741125methyl 2-methyl-1-(1-phenylethyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylateYield 31.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cooled (0° C.) solution of methyl 2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (1.02 g, 5.36 mmol) in N,N-dimethylformamide (20 mL) was added sodium hydride (60% w/w, 236 mg, 5.90 mmol). The resultant mixture was stirred for 15 minutes. Then (1-bromoethyl)benzene (2.00 g, 10.8 mmol) was added and the reaction was allowed to warm to room temperature. The reaction was maintained at ambient temperature for 12 hours. The reaction mixture was poured into saturated ammonium chloride solution (100 mL) with stirring. The mixture was extracted with ethyl acetate (200 mL×2) and the combined organic phase was washed with brine, dried over magnesium sulfate, filtered, and concentrated to give crude product which was purified by column chromatography (petroleum ether/ethyl acetate=20:1) to afford methyl 2-methyl-1-(1-phenylethyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (500 mg, 31.7%) as a viscous oil. 1H NMR (300 MHz, CD3OD): δ 8.38-8.35 (m, 1H), 8.25-8.23 (m, 1H), 7.30-7.14 (m, 6H), 6.55-6.48 (m, 1H), 3.88 (s, 3H), 2.54 (s, 3H), 2.02 (d, J=7.2 Hz, 3H).

Workup

  1. temperatureThe reaction was maintained at ambient temperature for 12 hours
  2. extractionThe mixture was extracted with ethyl acetate (200 mL×2)
  3. washthe combined organic phase was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give crude product which
  8. customwas purified by column chromatography (petroleum ether/ethyl acetate=20:1)

Sources & evidence

ORD record
ord-b524f20b312548aeb510b888f4fcf985
Source dataset
uspto-grants-2016_06
Patent number
US09371331B2

Reaction notes

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