Imidazole → alpha-(3,4-Dimethoxyphenyl)-1,3-dihydro-5-[2-(1H-imidazol-1-yl)ethoxy]-6-methoxy-alpha-[(4-methylphenyl)-thio]-2H-isoindole-2-heptanenitrile

HRID 863911Notes

Reaction equation

HRID 863911 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].Cl[CH2:9][CH2:10][O:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][C:20]=1[O:21][CH3:22])[CH2:17][N:16]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][C:28]([C:39]1[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[C:41]([O:47][CH3:48])[CH:40]=1)([S:31][C:32]1[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=1)[C:29]#[N:30])[CH2:15]2.[I-].[Na+]>CN(C)C=O.C1(C)C=CC=CC=1.O>[CH3:48][O:47][C:41]1[CH:40]=[C:39]([C:28]([S:31][C:32]2[CH:33]=[CH:34][C:35]([CH3:38])=[CH:36][CH:37]=2)([CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][N:16]2[CH2:15][C:14]3[C:18](=[CH:19][C:20]([O:21][CH3:22])=[C:12]([O:11][CH2:10][CH2:9][N:1]4[CH:5]=[CH:4][N:3]=[CH:2]4)[CH:13]=3)[CH2:17]2)[C:29]#[N:30])[CH:44]=[CH:43][C:42]=1[O:45][CH3:46]

Participants

8

Reactant 4

HCID 795ImidazoleHCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 107460535-(2-Chloroethoxy)-alpha-(3,4-dimethoxyphenyl)-1,3-dihydro-6-methoxy-alpha-[[4-methylphenyl)thio]-2H-isoindole-2-heptanenitrile

Product 1

HCID 10699180alpha-(3,4-Dimethoxyphenyl)-1,3-dihydro-5-[2-(1H-imidazol-1-yl)ethoxy]-6-methoxy-alpha-[(4-methylphenyl)-thio]-2H-isoindole-2-heptanenitrile

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 0.11 g of imidazole in 6 mL of N,N-dimethylformamide, under argon, is added 0.036 g of 60% of sodium hydride in oil. After stirring for 40 minutes, a solution of 0.3 g of 5-(2-chloroethoxy)-α-(3,4-dimethoxyphenyl)-1,3-dihydro-6-methoxy-α-[(4-methylphenyl)thio]-2H-isoindole-2-heptanenitrile in 8 mL of toluene is added followed by 0.3 g of sodium iodide. The resulting solution is heated at 75° C. for 21 hours. The solution is cooled and and poured into water. The solution is extracted with ethyl acetate and the organic layer washed with brine and dried over sodium sulfate. The solvent is removed at reduce pressure and the residual oil purified via column chromatography using a gradient elution from 4% methyl alcohol in methylene chloride to 9% methyl alcohol in methylene chloride. This affords 0.196 g of the desired product as a beige oil.

Workup

  1. temperatureThe solution is cooled
  2. extractionThe solution is extracted with ethyl acetate
  3. washthe organic layer washed with brine
  4. dry with materialdried over sodium sulfate
  5. customThe solvent is removed
  6. customthe residual oil purified via column chromatography
  7. washa gradient elution from 4% methyl alcohol in methylene chloride to 9% methyl alcohol in methylene chloride

Sources & evidence

ORD record
ord-4bcb7cafa20346af9b3f0fbcfa3c51ac
Source dataset
uspto-grants-1996_10
Patent number
US05561141

Reaction notes

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