4-Azaindole → 4-(5-Chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-pyrrolo [3,2-b]pyridin-1-ylmethylpentan-2-ol

HRID 400690Notes

Reaction equation

HRID 400690 reaction equation
[NH:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].[Cl:12][C:13]1[CH:14]=[C:15]([C:22]([CH3:32])([CH3:31])[CH2:23][C:24]2([C:27]([F:30])([F:29])[F:28])[CH2:26][O:25]2)[C:16]2[O:20][CH2:19][CH2:18][C:17]=2[CH:21]=1>CN(C=O)C.C(OCC)(=O)C>[Cl:12][C:13]1[CH:14]=[C:15]([C:22]([CH3:32])([CH3:31])[CH2:23][C:24]([CH2:26][N:1]2[C:9]3[C:4](=[N:5][CH:6]=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)([OH:25])[C:27]([F:28])([F:29])[F:30])[C:16]2[O:20][CH2:19][CH2:18][C:17]=2[CH:21]=1

Participants

6

Reactant 3

HCID 92264-AzaindoleHCID 24758Sodium hydrideHCID 600263575-Chloro-7-[1,1-dimethyl-2-(2-trifluoromethyloxiranyl)ethyl]-2,3-dihydrobenzofuran

Product 1

HCID 114192624-(5-Chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-pyrrolo [3,2-b]pyridin-1-ylmethylpentan-2-olYield 45%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1H-pyrrolo[3,2-b]pyridine (33.0 mg, 0.279 mmol) in 4 mL of DMF was treated with NaH (60% in mineral oil, 16.8 mg, 0.419 mmol) at room temperature. After 30 minutes, 5-chloro-7-[1,1-dimethyl-2-(2-trifluoromethyloxiranyl)ethyl]-2,3-dihydrobenzofuran (188 mg, 0.558 mmol) was added and the resulting mixture was stirred overnight. The reaction was then diluted with 5 mL of ethyl acetate and quenched with 5 mL of saturated ammonium chloride solution. The aqueous layer was extracted with 5 mL of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was triturated with diethyl ether to afford 55.0 mg (45% yield) of the title product as white solid.

Workup

  1. customquenched with 5 mL of saturated ammonium chloride solution
  2. extractionThe aqueous layer was extracted with 5 mL of ethyl acetate
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-07b93d38d29d433087c39ef056b6d833
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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