4-Chlorophenyl Isocyanate → HCID 21708709, compound
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]=1Participants
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 Method A above to obtain 1.1 g of the title product as a solid. 1H NMR (CD3SOCD3): δ11.68 (s, 1 H), 8.90 (s, 1 H), 8.10 (d, J =2 Hz, 1 H), 7.72 (d, J=9 Hz, 1 H), 7.66 (d, J =3 Hz, 1 H), 7.58 (dd, J =3, 9 Hz, 1 H), 7.40 (d, J =9 Hz, 2 H), 7.28 (d, J =9 Hz, 2 H), 6.60 (d, J =2 Hz, 1 H). Analysis for C15H12ClN3O3S:
Sources & evidence
- ORD record
- ord-51a8b884e9b54d47a57ec2407fbbeb05
- Source dataset
- uspto-grants-1992_12
- Patent number
- US05169860
Reaction notes
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