Isopropyl isocyanate → 3-Chloro-4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-N-(isopropylcarbamoyl)benzenesulfonamide

HRID 1627276Notes

Reaction equation

HRID 1627276 reaction equation
[Cl-].[Cl-].[Cl-].[Al+3].[CH:5]([N:8]=[C:9]=[O:10])([CH3:7])[CH3:6].[Cl:11][C:12]1[CH:13]=[C:14]([S:43]([NH2:46])(=[O:45])=[O:44])[CH:15]=[CH:16][C:17]=1[CH2:18][S:19][C:20]1[N:21]([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)[C:22]([C:25]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=2)([CH3:27])[CH3:26])=[CH:23][N:24]=1>C1(C)C=CC=CC=1>[Cl:11][C:12]1[CH:13]=[C:14]([S:43]([NH:46][C:9](=[O:10])[NH:8][CH:5]([CH3:7])[CH3:6])(=[O:45])=[O:44])[CH:15]=[CH:16][C:17]=1[CH2:18][S:19][C:20]1[N:21]([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)[C:22]([C:25]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=2)([CH3:27])[CH3:26])=[CH:23][N:24]=1

Participants

5

Reactant 3

HCID 61277Isopropyl isocyanateHCID 6451240Aluminum(III) ChlorideHCID 667400293-Chloro-4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)benzenesulfonamide

Product 1

HCID 667399383-Chloro-4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-N-(isopropylcarbamoyl)benzenesulfonamideYield 43.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of aluminum trichloride (75 mg, 513 μmol, 3.0 eq) in toluene (1 mL, anhyd) was added isopropylisocyanate (17 μL, 170 μmol, 1.0 eq). After 3 min of stirring at room temperature, 3-chloro-4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)benzenesulfonamide (100 mg, 170 μmol, 1.0 eq) was added neat. The reaction mixture was heated at 80° C. for 16 h, then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (3×), washed with water, brine, then dried and concentrated. Purification (silica gel chromatography, 20% methanol/ethyl acetate) provided the title compound (50 mg) as an off-white foam. 1H NMR (DMSO-d6, 400 MHz): δ 8.33 (s, 1H), 7.78 (s, 1H), 7.63 (d, J=7.8 Hz, 1H), 7.43 (d, J=8.2 Hz, 1H), 7.31 (d, J=8.2 Hz, 1H), 7.22 (s, 1H), 6.98-6.87 (m, 4H), 6.41-6.35 (m, 2H), 6.05 (br s, 1H), 4.22 (s, 2H), 3.61-3.50 (m, 1H), 1.44 (s, 6H), 0.97 (d, J=6.6 Hz, 6H); MS (EI) m/z 671 (MH)+.

Workup

  1. temperatureThe reaction mixture was heated at 80° C. for 16 h
  2. custompartitioned between ethyl acetate and water
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×)
  4. washwashed with water, brine
  5. customdried
  6. concentrationconcentrated
  7. customPurification (silica gel chromatography, 20% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-f73c3b9f24524977acfbba8cf94dc689
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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