Benzimidazole → HCID 68488860, compound

HRID 1991210Notes

Reaction equation

HRID 1991210 reaction equation
CC(C)([O-])C.[K+].[NH:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[CH:8]1.Br[CH:17]([CH3:31])[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([CH:17]([CH3:31])[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:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[CH:8]1

Participants

6

Reactant 3

HCID 5798BenzimidazoleHCID 23665647Potassium tert-butoxideHCID 68487715HCID 68487715, compound

Product 1

HCID 68488860HCID 68488860, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A solution of potassium tert-butoxide (0.25 mL of 1 M solution in THF, 0.25 mmol) was added to a solution of 1H-benzoimidazole (30 mg, 0.25 mmol) in anhydrous dioxane (10 mL) and anhydrous DMF (1 mL) under argon at ambient temperature. The mixture was stirred for 5 min before a solution of bromo-N-(3-trifluoromethyl-phenyl)-propionamide (59 mg, 0.2 mmol) in anhydrous dioxane (3 mL) was added. The mixture was stirred for 4 h, filtered and concentrated in vacuum. The crude product was purified on a preparative HPLC (XTerra C8 column 19×300 mm, 0.1 M aqueous NH4Ac/CH3CN). Product-containing fractions were pooled and lyophilized to afford 40 mg (60%) of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 1.8 (d, J=7.1 Hz, 3H), 5.1 (q, J=7.4 Hz, 1 H), 7.2 (m, 4 H), 7.4 (d, J=7.1 Hz, 1H), 7.5 (m, 2H,) 7.7 (m, 1H), 7.9 (s, 1H), 1/02 (s, 1 H).

Workup

  1. additionwas added
  2. filtrationfiltered
  3. concentrationconcentrated in vacuum
  4. customThe crude product was purified on a preparative HPLC (XTerra C8 column 19×300 mm, 0.1 M aqueous NH4Ac/CH3CN)

Sources & evidence

ORD record
ord-e8a24231700c4e9ca8d6ef4c9079da31
Source dataset
uspto-grants-2010_01
Patent number
US07645784B2

Reaction notes

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