4-(Chloromethyl)-1-trityl-1H-imidazole → 4-[6-(4-Cyano-phenyl)-2-oxo-3,3-bis-(1-trityl-1H-imidazol-4-ylmethyl)-2,3-dihydro-indol-1-ylmethyl]-N,N-dimethyl-benzenesulfonamide

HRID 1355661Notes

Reaction equation

HRID 1355661 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:17]=[C:16]3[C:12]([CH2:13][C:14](=[O:31])[N:15]3[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([S:25]([N:28]([CH3:30])[CH3:29])(=[O:27])=[O:26])=[CH:21][CH:20]=3)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)#[N:2].Cl[CH2:33][C:34]1[N:35]=[CH:36][N:37]([C:39]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:38]=1>C1COCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:17]=[C:16]3[C:12]([C:13]([CH2:33][C:34]4[N:35]=[CH:36][N:37]([C:39]([C:40]5[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=5)([C:46]5[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=5)[C:52]5[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=5)[CH:38]=4)([CH2:33][C:34]4[N:35]=[CH:36][N:37]([C:39]([C:52]5[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=5)([C:46]5[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=5)[C:40]5[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=5)[CH:38]=4)[C:14](=[O:31])[N:15]3[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([S:25]([N:28]([CH3:29])[CH3:30])(=[O:27])=[O:26])=[CH:21][CH:20]=3)=[CH:11][CH:10]=2)=[CH:7][CH:8]=1)#[N:2]

Participants

4

Reactant 2

HCID 27631764-(Chloromethyl)-1-trityl-1H-imidazoleHCID 185077664-[6-(4-Cyano-phenyl)-2-oxo-2,3-dihydro-indol-1-ylmethyl]-N,N-dimethyl-benzenesulfonamide

Product 1

HCID 867590514-[6-(4-Cyano-phenyl)-2-oxo-3,3-bis-(1-trityl-1H-imidazol-4-ylmethyl)-2,3-dihydro-indol-1-ylmethyl]-N,N-dimethyl-benzenesulfonamideYield 55.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-[6-(4-Cyano-phenyl)-2-oxo-2,3-dihydro-indol-1-ylmethyl]-N,N-dimethyl-benzenesulfonamide (216 mg, 0.501 mmol) and 4-chloromethyl-1-trityl-1H-imidazole compound (402 mg, 1.12 mmol) were dissolved in 5 ml of anhydrous THF under an atmosphere of dry N2. To this solution was added 95% potassium hexamethyldisilylamide (KHMDS) (230 mg, 1.10 mmol) and the reaction mixture was subsequently stirred overnight. The reaction mixture was partitioned between DCM and saturated aqueous NaHCO3. The DCM layer was dried over sodium sulfate (Na2SO4), filtered and concentrated under vacuum to give a purple foam which was chromatographed on flash silica gel eluting with a gradient of chloroform (CHCl3) to CHCl3/MeOH/NH4OH (98/2/0.01) to give 300 mg of the titled compound as a pink oil.

Workup

  1. customThe reaction mixture was partitioned between DCM and saturated aqueous NaHCO3
  2. dry with materialThe DCM layer was dried over sodium sulfate (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customto give a purple foam which
  6. customwas chromatographed on flash silica gel eluting with a gradient of chloroform (CHCl3) to CHCl3/MeOH/NH4OH (98/2/0.01)

Sources & evidence

ORD record
ord-6949ed96647d4bf0805c89b12c89ee9c
Source dataset
uspto-grants-2003_07
Patent number
US06586447B1

Reaction notes

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