Dimethylformamide → N-[(5-chloro-1-methyl-1H-benzimidazol-2-yl)methyl]-2-(5-chloro-2-oxo-1,3-benzothiazol-3 (2H)-yl)-N-methylacetamide hydrochloride

HRID 1428410Notes

Reaction equation

HRID 1428410 reaction equation
[H-].[Na+].[CH3:3]N(C=O)C.[Cl:8][C:9]1[CH:34]=[CH:33][C:12]2[NH:13][C:14]([CH2:16][N:17]([CH3:32])[C:18](=[O:31])[CH2:19][N:20]3[C:24]4[CH:25]=[C:26]([Cl:29])[CH:27]=[CH:28][C:23]=4[S:22][C:21]3=[O:30])=[N:15][C:11]=2[CH:10]=1.CI>O>[ClH:8].[Cl:8][C:9]1[CH:34]=[CH:33][C:12]2[N:13]([CH3:3])[C:14]([CH2:16][N:17]([CH3:32])[C:18](=[O:31])[CH2:19][N:20]3[C:24]4[CH:25]=[C:26]([Cl:29])[CH:27]=[CH:28][C:23]=4[S:22][C:21]3=[O:30])=[N:15][C:11]=2[CH:10]=1

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178483012HCID 178483012, compound

Product 1

HCID 117652655N-[(5-chloro-1-methyl-1H-benzimidazol-2-yl)methyl]-2-(5-chloro-2-oxo-1,3-benzothiazol-3 (2H)-yl)-N-methylacetamide hydrochloride

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Under a nitrogen gas flow, to a mixture of NaH (55% in oil, 35 mg) and DMF (4 mL) was added a mixture of N-[(5-chloro-1H-benzimidazol-2-yl)methyl]-2-(5-chloro-2-oxo-1,3-benzothiazol-3(2H)-yl)-N-methylacetamide (335 mg) and DMF (10 mL) under ice-cooling, followed by stirring at room temperature for 30 minutes. The reaction mixture was ice-cooled and methyl iodide (55 μL) was added thereto, followed by stirring at room temperature overnight. The reaction mixture was added to water, followed by extraction with EtOAc. The organic layer was washed with brine and dried over Na2SO4, and then concentrated under reduced pressure. To the residue was added chloroform. The resulting solid was collected and then washed with chloroform. To a mixture of the obtained solid and MeOH (3 mL) was added 4 M hydrogen chloride/EtOAc (300 μL), followed by stirring at room temperature. The reaction mixture was concentrated under reduced pressure, and to the residue was added EtOAc. The resulting solid was collected and then washed with EtOAc to obtain N-[(5-chloro-1-methyl-1H-benzimidazol-2-yl)methyl]-2-(5-chloro-2-oxo-1,3-benzothiazol-3(2H)-yl)-N-methylacetamide hydrochloride (60 mg).

Workup

  1. additionwas added
  2. temperaturecooling
  3. temperaturecooled
  4. stirringby stirring at room temperature overnight
  5. extractionfollowed by extraction with EtOAc
  6. washThe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. additionTo the residue was added chloroform
  10. customThe resulting solid was collected
  11. washwashed with chloroform
  12. additionTo a mixture of the obtained solid and MeOH (3 mL)
  13. additionwas added 4 M hydrogen chloride/EtOAc (300 μL)
  14. stirringby stirring at room temperature
  15. concentrationThe reaction mixture was concentrated under reduced pressure
  16. additionto the residue was added EtOAc
  17. customThe resulting solid was collected
  18. washwashed with EtOAc

Sources & evidence

ORD record
ord-eec89834c44e4379accad58d28012a2d
Source dataset
uspto-grants-2015_01
Patent number
US08937087B2

Reaction notes

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