Sodium hydride → 4-(3,4-Dihydro-2H-chromen-4-yloxy)-N,N,1,2-tetramethyl-1H-benzimidazole-6-carboxamide

HRID 2238579Notes

Reaction equation

HRID 2238579 reaction equation
[OH:1][C:2]1[C:10]2[N:9]=[C:8]([CH3:11])[N:7]([CH3:12])[C:6]=2[CH:5]=[C:4]([C:13]([N:15]([CH3:17])[CH3:16])=[O:14])[CH:3]=1.[H-].[Na+].Cl[CH:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[O:24][CH2:23][CH2:22]1>CN(C)C=O>[O:24]1[C:25]2[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:21]([O:1][C:2]2[C:10]3[N:9]=[C:8]([CH3:11])[N:7]([CH3:12])[C:6]=3[CH:5]=[C:4]([C:13]([N:15]([CH3:16])[CH3:17])=[O:14])[CH:3]=2)[CH2:22][CH2:23]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 127921574-ChlorochromanHCID 534710164-Hydroxy-N,N,1,2-tetramethyl-1H-benzimidazole-6-carboxamide

Product 1

HCID 593038964-(3,4-Dihydro-2H-chromen-4-yloxy)-N,N,1,2-tetramethyl-1H-benzimidazole-6-carboxamideYield 52.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

To a stirred suspension of 4-hydroxy-N,N,1,2-tetramethyl-1H-benzimidazole-6-carboxamide (50 mg, 0.21 mmol, WO 2004054984) in N,N-dimethylformamide (2 mL) was added sodium hydride (60% dispersion in mineral oil, 11 mg, 0.27 mmol) at room temperature. After stirring for 20 minutes, a solution of 4-chlorochromane (71 mg, 0.42 mmol, WO 2000078751) in N,N-dimethylformamide (1 mL) was added at room temperature. The reaction mixture was warmed to 70° C., and stirred for 6 hours at the same temperature. The reaction mixture was quenched with sodium hydrogencarbonate aqueous solution, and extracted with ethyl acetate (20 mL×2). The combined extracts were washed with water and brine, dried over magnesium sulfate, and concentrated in vacuum. The residue was purified by column chromatography on silica gel (ethyl acetate:methanol=10:1 as an eluent) to afford the title compound as a white solid (40 mg, 52%):

Workup

  1. stirringstirred for 6 hours at the same temperature
  2. customThe reaction mixture was quenched with sodium hydrogencarbonate aqueous solution
  3. extractionextracted with ethyl acetate (20 mL×2)
  4. washThe combined extracts were washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuum
  7. customThe residue was purified by column chromatography on silica gel (ethyl acetate

Sources & evidence

ORD record
ord-6b7509b4db3a4ce399f3008ddcf73e92
Source dataset
uspto-grants-2010_05
Patent number
US07718809B2

Reaction notes

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