Indole → HCID 725887, compound

HRID 1991230Notes

Reaction equation

HRID 1991230 reaction equation
CC(C)([O-])C.[K+].[NH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8]1.Br[CH2:17][C:18]([NH:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=1)=[O:19]>O1CCOCC1.CN(C=O)C>[N:7]1([CH2:17][C:18]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:29])[F:30])[CH:22]=2)=[O:19])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8]1

Participants

6

Reactant 3

HCID 798IndoleHCID 23171522-bromo-N-[3-(trifluoromethyl)phenyl]acetamideHCID 23665647Potassium tert-butoxide

Product 1

HCID 725887HCID 725887, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

A solution of potassium tert-butoxide (0.25 mmol) in TBF (0.25 mL) was added to a solution of 1H-indole (30 mg, 0.25 mmol) in a mixture of dioxane (6 m]L) and DMF (1.5 mL) under argon atmosphere at ambient temperature. The solution was stirred for 5 min before a solution of 2-bromo-N-(3-trifluoromethyl-phenyl)-acetamide (0.2 mmol) in DMF (1 mL) was added dropwise. The reaction mixture was stirred overnight at ambient temperature and the solvents were-removed in vacuum. The crude product was purified on a preparative LC/MS (XTerra C8 column 19×100 mm, 0.1 M aqueous NH4Ac/CH3CN). The product-containing fractions were pooled and lyophilized to afford 24 mg (38%) of the title compound. Calculated for C17H13F3N2O m/z: 318.3, found 319.0 [M+H]+. 1H NMR (400 MHz, CDCl3) δ ppm 4.9 (s, 2H), 6.7 (d, J=3.0 Hz, 1H), 7.0 (s, 1H), 7.1 (d, J=3.0 Hz, 1H), 7.2-7.3 (m, 5 H), 7.4 (m, 1H), 7.6 (s, 1H), 7.7 (d, J=8.1 Hz, 1H).

Workup

  1. additionwas added dropwise
  2. customthe solvents were-removed in vacuum
  3. customThe crude product was purified on a preparative LC/MS (XTerra C8 column 19×100 mm, 0.1 M aqueous NH4Ac/CH3CN)

Sources & evidence

ORD record
ord-b98ada7517ab4eb9857c1e2ab7dffbe2
Source dataset
uspto-grants-2010_01
Patent number
US07645784B2

Reaction notes

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