Sodium hydride → HCID 14622528, compound

HRID 1639011Notes

Reaction equation

HRID 1639011 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[O:15][CH2:16][C:17]([F:20])([F:19])[F:18])[C:11]([CH2:21][S:22][C:23]1[NH:24][C:25]3[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=3[N:27]=1)=[N:10][CH:9]=[CH:8]2.[C:32]([O:38][CH2:39]Cl)(=[O:37])[C:33]([CH3:36])([CH3:35])[CH3:34]>CN(C=O)C>[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[O:15][CH2:16][C:17]([F:19])([F:20])[F:18])[C:11]([CH2:21][S:22][C:23]1[N:24]([CH2:39][O:38][C:32](=[O:37])[C:33]([CH3:36])([CH3:35])[CH3:34])[C:25]3[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=3[N:27]=1)=[N:10][CH:9]=[CH:8]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 87885Chloromethyl pivalateHCID 14622474HCID 14622474, compound

Product 1

HCID 14622528HCID 14622528, compoundYield 92.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 30.8 mg of 60% NaH (0.77 mmol) in 5 ml of dry DMF was added 293.6 mg of 2-{[6-methoxy-7-(2,2,2-trifluoroethoxy)isoquinolin-1-yl]methylthio}benzimidazole (Ia-7) (0.7 mmol) and the mixture was stirred for 10 min. at room temperature. The mixture was mixed with 126.5 mg of chloromethyl pivalate, stirred for 2 hr. at room temperature and allowed to stand overnight. After DMF was distilled off in vacuo, the residue was mixed with water and extracted with CH2Cl2. The CH2Cl2 layer was dried over anhydrous sodium sulfat4e and concentrated. The residue was subjected to silica gel column chromatography, eluting with CH2Cl2 -AcOEt. Crude product was washed with cyclohexane to give 344.7 mg of the objective compound 2-{[6-methoxy-7-(2,2,2-trifluoroethoxy)isoquinolin-1-yl]methylthio}-1-pivaloyloxymethylbenzimidazole (Ib-10) (Yield: 92.3%).

Workup

  1. stirringstirred for 2 hr
  2. customat room temperature
  3. waitto stand overnight
  4. distillationAfter DMF was distilled off in vacuo
  5. additionthe residue was mixed with water
  6. extractionextracted with CH2Cl2
  7. dry with materialThe CH2Cl2 layer was dried over anhydrous sodium sulfat4e
  8. concentrationconcentrated
  9. washeluting with CH2Cl2 -AcOEt
  10. washCrude product was washed with cyclohexane

Sources & evidence

ORD record
ord-602010dc4c234c40b15ad401e393bb8f
Source dataset
uspto-grants-1989_11
Patent number
US04882338

Reaction notes

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