4-Chlorophenyl Isocyanate → HCID 21708709, compound

HRID 326687Notes

Reaction equation

HRID 326687 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([S:10]([NH2:13])(=[O:12])=[O:11])[CH:8]=2)[CH:3]=[CH:2]1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]=[C:22]=[O:23])=[CH:17][CH:16]=1>>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]([NH:13][S:10]([C:7]2[CH:8]=[C:9]3[C:4]([CH:3]=[CH:2][NH:1]3)=[CH:5][CH:6]=2)(=[O:11])=[O:12])=[O:23])=[CH:17][CH:16]=1

Participants

3

Reactant 2

HCID 76934-Chlorophenyl IsocyanateHCID 217087211H-Indole-6-sulfonamide

Product 1

HCID 21708709HCID 21708709, compoundYield 51.6%

Procedure

To a solution of 4-chloro-3-nitrophenylsulfonamide (12 g, 51 mmol) dissolved in 50 ml of anhydrous dimethylformamide, was added 13.1 g (116 mmol) of ethylcyanoacetate and 10.5 g (76 mmol) of anhydrous potassium carbonate. This mixture was heated at 110° C. for 3 hours, cooled to room temperature, and added to ice water containing 8 ml of concentrated sulfuric acid. The mixture was extracted with ethyl acetate (3×200 ml), and the combined organic layer was back extracted with 200 ml of water. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. Purification by a preparative high pressure liquid chromatogram (Waters Prep 500 A) with 55% ethyl acetate in hexanes on a silica gel cartridge. The product was added to 45 ml of 50% aqueous acetic acid containing 3 ml of concentrated sulfuric acid and refluxed for 12 hours. The reaction was cooled to room temperature and added to 400 ml water. This mixture was extracted with ethyl acetate (3×100 ml). The combined organic layer was dried with anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was crystallized from 40 ml of ethyl acetate, 3 ml of ethanol and 1 ml of hexanes to obtain 6.9 g of 3-nitro-4-(2-acetonitrile)phenyl sulfonamide. This material was dissolved in 40 ml of ethanol containing 3 g of 5% palladium on activated carbon. This mixture was placed in a Parr Hydrogenation apparatus with 60 p.s.i. of hydrogen at 40° C. for 3 hours. This mixture was filtered, the filtrate concentrated under vacuum, and the residue recrystallized from 20 ml of ethyl acetate and 10 ml of ethanol to obtain 2.4 g of 6-indolesulfonamide. The sulfonamide (6.1 mmol) was reacted with 4-chlorophenylisocyanate (6.1 mmol) as described in Preparation 2 supra to obtain 1.1 g of the title product as a solid.

Workup

  1. customas described in Preparation 2 supra

Sources & evidence

ORD record
ord-673680ee0de640598c8b1b42ecce2189
Source dataset
uspto-grants-1993_12
Patent number
US05270329

Reaction notes

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