Water → HCID 71261271, compound

HRID 2411493Notes

Reaction equation

HRID 2411493 reaction equation
C(O[C:6](=O)[NH:7][C:8]1[CH:13]=[C:12]([N:14]2[CH2:18][CH2:17][CH2:16][S:15]2(=[O:20])=[O:19])[CH:11]=[CH:10][C:9]=1[C:21]([N:23]1[CH2:28][CH2:27][N:26]([C:29]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][C:30]=2[CH3:36])[CH2:25][CH2:24]1)=[O:22])(C)(C)C.[H-].[Na+].CI.O>CN(C)C=O>[CH3:36][C:30]1[CH:31]=[C:32]([CH3:35])[CH:33]=[CH:34][C:29]=1[N:26]1[CH2:25][CH2:24][N:23]([C:21]([C:9]2[CH:10]=[CH:11][C:12]([N:14]3[CH2:18][CH2:17][CH2:16][S:15]3(=[O:20])=[O:19])=[CH:13][C:8]=2[NH:7][CH3:6])=[O:22])[CH2:28][CH2:27]1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 71252503HCID 71252503, compound

Product 1

HCID 71261271HCID 71261271, compoundYield 7.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

[2-Amino-4-(1,1-dioxo-1λ6-isothiazolidin-2-yl)phenyl][4-(2,4-dimethylphenyl)piperazin-1-yl]methanone (210 mg) described in Example 103 was dissolved in dichloromethane (2 mL), 4-dimethylaminopyridine (0.3 mg) and di-tert-butyl dicarbonate (110 mg) were added, and the mixture was stirred at room temperature. After completion of the reaction, the solvent was evaporated, and the obtained residue was purified by column chromatography (chloroform:methanol) to give {2-[4-(2,4-dimethylphenyl)piperazine-1-carbonyl]-5-(1,1-dioxo-1λ6-isothiazolidin-2-yl)phenyl}carbamic acid tert-butyl ester (283 mg). The obtained {2-[4-(2,4-dimethylphenyl)piperazine-1-carbonyl]-5-(1,1-dioxo-1λ6-isothiazolidin-2-yl)phenyl}carbamic acid tert-butyl ester (282.6 mg) was dissolved in N,N-dimethylformamide (8 mL), sodium hydride (26 mg) was added, and the mixture was stirred at room temperature for 10 min. Methyl iodide (0.04 mL) was added, and the mixture was stirred at room temperature. After completion of the reaction, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained residue was dissolved in 1,4-dioxane (1 mL), 4N hydrogen chloride/1,4-dioxane (2.6 mL) was added, and the mixture was stirred at room temperature for 2 hr. To the reaction mixture was added aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and the solvent was evaporated. The obtained residue was purified by HPLC (ODS, 0.05% TFA aqueous solution-acetonitrile) to give the title compound (17 mg).

Workup

  1. stirringthe mixture was stirred at room temperature
  2. additionwas added to the reaction mixture
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. customthe solvent was evaporated
  6. dissolutionThe obtained residue was dissolved in 1,4-dioxane (1 mL)
  7. addition4N hydrogen chloride/1,4-dioxane (2.6 mL) was added
  8. stirringthe mixture was stirred at room temperature for 2 hr
  9. additionTo the reaction mixture was added aqueous sodium hydrogen carbonate solution
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe organic layer was washed with water and saturated brine
  12. customthe solvent was evaporated
  13. customThe obtained residue was purified by HPLC (ODS, 0.05% TFA aqueous solution-acetonitrile)

Sources & evidence

ORD record
ord-fd117e40e20c46be842cb93beada4a7b
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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