Sodium hydride → tert-Butyl [3-(6-chloropyrimidin-4-yl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]acetate

HRID 1921173Notes

Reaction equation

HRID 1921173 reaction equation
[O:1]=[C:2]1[N:6]([CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:5]2[CH:15]=[CH:16][CH:17]=[CH:18][C:4]=2[NH:3]1.[H-].[Na+].[Cl:21][C:22]1[CH:27]=[C:26](Cl)[N:25]=[CH:24][N:23]=1>CN(C=O)C>[Cl:21][C:22]1[N:23]=[CH:24][N:25]=[C:26]([N:3]2[C:4]3[CH:18]=[CH:17][CH:16]=[CH:15][C:5]=3[N:6]([CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:2]2=[O:1])[CH:27]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 709434,6-DichloropyrimidineHCID 20814117Tert-butyl (2-oxo-2,3-dihydrobenzimidazol-1-yl)acetate2×

Product 1

HCID 86607781tert-Butyl [3-(6-chloropyrimidin-4-yl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of tert-butyl (2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)acetate (130 mg, 0.52 mmol, described in Intermediate 7) in DMF (0.7 mL) was added sodium hydride (15 mg of a 60% dispersion in mineral oil, 0.38 mmol). The mixture was stirred for 5 min, then 4,6-dichloropyrimidine (234 mg, 1.57 mmol) was added and argon was bubbled through the mixture for 5 min. The reaction mixture was heated at 140° C. for 10 min in a microwave reactor. The cooled mixture was partitioned between CHCl3 (10 mL) and saturated aqueous NaHCO3 (5 mL). The aqueous phase was extracted further with CHCl3 (10 mL), and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—95:5 to 75:25, to give the title compound. MS: m/z=361 (M+1).

Workup

  1. customargon was bubbled through the mixture for 5 min
  2. customThe cooled mixture was partitioned between CHCl3 (10 mL) and saturated aqueous NaHCO3 (5 mL)
  3. extractionThe aqueous phase was extracted further with CHCl3 (10 mL)
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by silica gel chromatography
  8. washeluting with a gradient of hexane

Sources & evidence

ORD record
ord-e53feec2bd904524a3f522f888e2c84e
Source dataset
uspto-grants-2012_05
Patent number
US08173655B2

Reaction notes

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