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

HRID 564825Notes

Reaction equation

HRID 564825 reaction equation
C([Li])CCC.[CH3:6][N:7]([CH3:16])[S:8]([N:11]1[CH:15]=[CH:14][N:13]=[CH:12]1)(=[O:10])=[O:9].Cl[Si:18]([CH2:23][CH3:24])([CH2:21][CH3:22])[CH2:19][CH3:20].[Cl:25][C:26]1[CH:51]=[CH:50][C:29]([C:30]([C:32]2[CH:33]=[C:34]3[C:39](=[CH:40][CH:41]=2)[N:38]([CH3:42])[C:37](=[O:43])[CH:36]=[C:35]3[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[O:31])=[CH:28][CH:27]=1>O1CCCC1>[Cl:25][C:26]1[CH:27]=[CH:28][C:29]([C:30]([C:32]2[CH:33]=[C:34]3[C:39](=[CH:40][CH:41]=2)[N:38]([CH3:42])[C:37](=[O:43])[CH:36]=[C:35]3[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)([OH:31])[C:14]2[N:13]=[C:12]([Si:18]([CH2:23][CH3:24])([CH2:21][CH3:22])[CH2:19][CH3:20])[N:11]([S:8]([N:7]([CH3:16])[CH3:6])(=[O:9])=[O:10])[CH:15]=2)=[CH:50][CH:51]=1

Participants

6

Reactant 4

HCID 13819ChlorotriethylsilaneHCID 395751N,N-Dimethyl-1H-imidazole-1-sulfonamideHCID 22714346HCID 22714346, compoundHCID 178418339Butyllithium2×

Product 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-sulfonamideYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °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. stirringthe mixture was stirred till the temperature
  2. customreached 20° C
  3. temperatureThe mixture was cooled till −78° C.
  4. stirringthe mixture was stirred at −78° C. for 1 hour
  5. customto reach −15° C
  6. temperatureThe mixture was cooled again till −78° C.
  7. stirringthe mixture was stirred till the temperature
  8. customreached 20° C
  9. extractionextracted with ethyl acetate
  10. dry with materialThe organic layer was dried (MgSO4)
  11. filtrationfiltered off
  12. customevaporated till dryness
  13. customThe product was used without further purification

Sources & evidence

ORD record
ord-ed0736d505b44b26999523f4d1f219b8
Source dataset
uspto-grants-2001_01
Patent number
US06169096A

Reaction notes

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