Sodium hydride → 8-(4-Fluorophenyl)-1-(isoxazol-3-ylmethyl)-N,N,2-trimethyl-1,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamide

HRID 1258473Notes

Reaction equation

HRID 1258473 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][C:11]3[C:14]([C:22]([N:24]([CH3:26])[CH3:25])=[O:23])=[CH:15][C:16]4[NH:17][C:18]([CH3:21])=[N:19][C:20]=4[C:10]=3[O:9]2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:30][C:31]1[CH:35]=[CH:34][O:33][N:32]=1>CN(C)C=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][C:11]3[C:14]([C:22]([N:24]([CH3:25])[CH3:26])=[O:23])=[CH:15][C:16]4[N:17]=[C:18]([CH3:21])[N:19]([CH2:30][C:31]5[CH:35]=[CH:34][O:33][N:32]=5)[C:20]=4[C:10]=3[O:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 104646163-(Bromomethyl)-1,2-oxazole2×HCID 672205608-(4-Fluorophenyl)-N,N,2-trimethyl-3,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamide

Product 1

HCID 248607638-(4-Fluorophenyl)-1-(isoxazol-3-ylmethyl)-N,N,2-trimethyl-1,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamideYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 8-(4-fluorophenyl)-N,N,2-trimethyl-3,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamide (50.0 mg, 0.141 mmol, Step 8 of Example 8) in N,N-dimethylformamide (1.4 mL), was added sodium hydride (6.7 mg, 0.17 mmol) at 0° C. and the mixture was stirred at 0° C. for 30 minutes. Then a solution of 3-(bromomethyl)isoxazole in N,N-dimethylformamide (1.0 mL, Step 1) was added to the mixture at 0° C. The mixture was allowed to warm to room temperature, stirred for 4 hours and left at the same temperature overnight. The reaction was quenched by saturated ammonium chloride aqueous solution. The mixture was extracted twice with ethyl acetate. The combined organic layer was washed with water and brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by preparative TLC eluting with hexane/ethyl acetate (1:1, twice), then dichloromethane/methanol (20:1, twice) to afford the title compound as a pale yellow solid (23.5 mg, 38%).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 4 hours
  3. waitleft at the same temperature overnight
  4. customThe reaction was quenched by saturated ammonium chloride aqueous solution
  5. extractionThe mixture was extracted twice with ethyl acetate
  6. washThe combined organic layer was washed with water and brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by preparative TLC
  10. washeluting with hexane/ethyl acetate (1:1

Sources & evidence

ORD record
ord-444101980cf94c8e8694a51443be9dd0
Source dataset
uspto-grants-2013_06
Patent number
US08466166B2

Reaction notes

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