Dimethylformamide → N-Benzyl-5-chloro-3-phenyl-2H-isoindole-1-carboxamide

HRID 1973316Notes

Reaction equation

HRID 1973316 reaction equation
[CH2:1]([N:8]1[C:14]2[CH:15]=[CH:16][C:17]([Cl:19])=[CH:18][C:13]=2[C:12]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:11][CH2:10][C:9]1=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C)C=O.[H-].[Na+]>O>[CH2:1]([NH:8][C:9]([C:10]1[NH:11][C:12]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:13]2[C:14]=1[CH:15]=[CH:16][C:17]([Cl:19])=[CH:18]2)=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 10570551HCID 10570551, compound

Product 1

HCID 54425733N-Benzyl-5-chloro-3-phenyl-2H-isoindole-1-carboxamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 36.1 g. of 1-benzyl-7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one in 300 ml. of dimethylformamide is treated under an atmosphere of argon at room temperature with 0.11 mol. of sodium hydride (4.8 g. of a 55% dispersion in mineral oil). The mixture is first heated to 60° C. over a period of about 30 minutes, and then stirred for 1 hour at this temperature for an additional 1 hour at 70° C. After cooling, 10 ml. of water are added dropwise and the mixture is poured into 3 liters of ice-water. After the addition of 100 g. of sodium chloride, the separated product is extracted with methylene chloride. The organic phase is washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated to dryness. The resulting oily residue is chromatographed on 1000 g. of silica gel with methylene chloride/ethyl acetate (4:1) as the eluant. The homogeneous fractions are combined, evaporated and triturated with a small amount of ether, and there is obtained 5-chloro-3-phenylisoindole-1-carboxylic acid benzylamide in the form of fibrous, greenish crystals; melting point 202°-204° C. (decomposition). Recrystallization from chloroform does not increase the melting point.

Workup

  1. temperatureAfter cooling
  2. additionAfter the addition of 100 g
  3. extractionof sodium chloride, the separated product is extracted with methylene chloride
  4. washThe organic phase is washed with a saturated solution of sodium chloride
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. customThe resulting oily residue is chromatographed on 1000 g
  8. customevaporated
  9. customtriturated with a small amount of ether

Sources & evidence

ORD record
ord-7d12b38a004a4652a4754b5dd11fd314
Source dataset
uspto-grants-1976_12
Patent number
US03996374

Reaction notes

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