(+/-)-4-[(4-chlorophenyl)(1,2-dihydro-1-methyl-2-oxo-4-phenyl-6-quinolinyl)hydroxymethyl]-N,N-dimethyl-2-(triethylsilyl)-1H-imidazole-1-sulfonamide → (+)-4-[(4-chlorophenyl)(1,2-dihydro-1-methyl-2-oxo-4-phenyl-6-quinolinyl)hydroxymethyl]-N,N-dimethyl-1H-imidazole-1-sulfonamide

HRID 564826Notes

Reaction equation

HRID 564826 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:28]2[CH:29]=[C:30]3[C:35](=[CH:36][CH:37]=2)[N:34]([CH3:38])[C:33](=[O:39])[CH:32]=[C:31]3[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)([OH:27])[C:9]2[N:10]=[C:11]([Si](CC)(CC)CC)[N:12]([S:14]([N:17]([CH3:19])[CH3:18])(=[O:16])=[O:15])[CH:13]=2)=[CH:4][CH:3]=1>S(=O)(=O)(O)O.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:28]2[CH:29]=[C:30]3[C:35](=[CH:36][CH:37]=2)[N:34]([CH3:38])[C:33](=[O:39])[CH:32]=[C:31]3[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)([OH:27])[C:9]2[N:10]=[CH:11][N:12]([S:14]([N:17]([CH3:18])[CH3:19])(=[O:15])=[O:16])[CH:13]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 22714347(+/-)-4-[(4-chlorophenyl)(1,2-dihydro-1-methyl-2-oxo-4-phenyl-6-quinolinyl)hydroxymethyl]-N,N-dimethyl-2-(triethylsilyl)-1H-imidazole-1-sulfonamide

Product 1

HCID 22714362(+)-4-[(4-chlorophenyl)(1,2-dihydro-1-methyl-2-oxo-4-phenyl-6-quinolinyl)hydroxymethyl]-N,N-dimethyl-1H-imidazole-1-sulfonamideYield 11.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1118Sulfuric AcidSolvent

Conditions

Temperature
110 °C

Procedure

Butyllithium (30.1 ml) was added slowly at −78° C. to a solution of N,N-dimethyl-1H-imidazol-1-sulfonamide (8,4 g) in tetrahydrofuran (150 ml) and the mixture was stirred at −78° C. for 15 minutes. Chlorotriethylsilane (8.1 ml) was added and the mixture was stirred till the temperature reached 20° C. The mixture was cooled till −78° C., butyllithium (30.1 ml) was added, the mixture was stirred at −78° C. for 1 hour and allowed to reach −15° C. The mixture was cooled again till −78° C., a solution of 6-(4-chlorobenzoyl)-1-methyl-4-phenyl-2(1 H)-quinolinone (15 g) in tetrahydrofuran (30 ml) was added and the mixture was stirred till the temperature reached 20° C. The mixture was hydrolized and extracted with ethyl acetate. The organic layer was dried (MgSO4), filtered off and evaporated till dryness. The product was used without further purification, yielding 26 g (100%) of (±)-4-[(4-chlorophenyl)(1,2-dihydro-1-methyl-2-oxo-4-phenyl-6-quinolinyl)hydroxymethyl]-N,N-dimethyl-2-(triethylsilyl)-1H-imidazole-1-sulfonamide (intern. 3-a). A mixture of intermediate (3-a) (26 g) in sulfuric acid (2.5 ml) and water (250 ml) was stirred and heated at 110° C. for 2 hours. The mixture was poured into ice, basified with NH4 and extracted with DCM. The organic layer was dried (MgSO4), filtered off and evaporated till dryness. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 99/1/0.2). The pure fractions were collected and evaporated, yielding 2.4 g (11%) of (±)-4-[(4-chlorophenyl)(1,2-dihydro-1-methyl-2-oxo-4-phenyl-6-quinolinyl)hydroxymethyl]-N,N-dimethyl-1H-imidazole 1-sulfonamide (interm. 3-b).

Workup

  1. additionThe mixture was poured into ice
  2. extractionextracted with DCM
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered off
  5. customevaporated till dryness
  6. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 99/1/0.2)
  7. customThe pure fractions were collected
  8. customevaporated

Sources & evidence

ORD record
ord-98c6a923eda445839a1cf9166a7b2643
Source dataset
uspto-grants-2001_01
Patent number
US06169096A

Reaction notes

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