p-Toluenesulfonic acid → 1-methyl-3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3yl]-1H-indole-5-carbonitrile

HRID 342060

Reaction equation

HRID 342060 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]#[N:12])=[CH:8][CH:9]=2)[CH:4]=[CH:3]1.[C:13](Cl)(=O)[C:14](Cl)=[O:15].Cl.C([O:23][C:24](=[NH:36])[CH2:25][C:26]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[N:28]([CH3:35])[CH:27]=1)(C)C.C(N(CC)CC)C.CCN(CC)CC.CC1C=CC(S(O)(=O)=O)=CC=1>C(OCC)C.C(Cl)Cl.C1(C)C=CC=CC=1>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]#[N:12])=[CH:8][CH:9]=2)[C:4]([C:13]2[C:14](=[O:15])[NH:23][C:24](=[O:36])[C:25]=2[C:26]2[C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[N:28]([CH3:35])[CH:27]=2)=[CH:3]1

Participants

9

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 65578Oxalyl chlorideHCID 114125131-methyl-1H-indole-5-carbonitrileHCID 22592508triethylamine TriethylamineHCID 22907276Isopropyl 1-methyl-3-indoleacetimidate hydrochloride

Product 1

HCID 193540561-methyl-3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3yl]-1H-indole-5-carbonitrile

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

1-methyl-1H-indole-5-carbonitrile, a known compound, (0.4 g, 2.55 mmole) was dissolved in ethyl ether (25 mL), chilled in an ice bath and treated with oxalyl chloride (0.35 mL, 4.0 mmole, 1.6 equiv.). This mixture was stirred at room temperature overnight, then the solvent was removed by evaporation, and evaporated from CH2Cl2 again. This residue along with 2-(1-methyl-1H-indol-3yl)-acetimidic acid isopropyl ester hydrochloride (0.68 g, 2.55 mmole, 1 equiv.) was suspended in CH2Cl2 (50 mL) and cooled in an ice bath. The mixture was treated with triethylamine Et3N (1.4 mL, 10 mmole, 4 equiv.) stirred at 0° for 30 minutes, then at room temperature for an additional 3 hours. The reaction mixture was then diluted with CH2Cl2 (100 mL), washed with H2O (25 mL), and then 0.5N HCl (25 mL). The organic fractions were dried over MgSO4, filtered and evaporated to give a dark oil. The residue was taken up in toluene (50 mL), chilled in an ice bath, then treated with pTsOH (0.53 g, 2.8 mmole, 1.1 equiv.), then stirred at room temperature overnight. The toluene was evaporated, and the residue dissolved in CH2Cl2 (100 mL), then washed with saturated NaHCO3 (30 mL), H2O (30 mL), and brine (30 mL). The organic layer was dried over MgSO4, filtered and evaporated, then purified by flash column chromatography (10% ethyl acetate (EtOAc)/Hexane). The product was further purified by washing with cold CH2Cl2 to provide 0.43 g of 1-methyl-3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3yl]-1H-indole-5-carbonitrile.

Workup

  1. temperaturechilled in an ice bath
  2. customthe solvent was removed by evaporation
  3. customevaporated from CH2Cl2 again
  4. temperaturecooled in an ice bath
  5. stirringstirred at 0° for 30 minutes
  6. waitat room temperature for an additional 3 hours
  7. washwashed with H2O (25 mL)
  8. dry with materialThe organic fractions were dried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customto give a dark oil
  12. temperaturechilled in an ice bath
  13. stirringstirred at room temperature overnight
  14. customThe toluene was evaporated
  15. dissolutionthe residue dissolved in CH2Cl2 (100 mL)
  16. washwashed with saturated NaHCO3 (30 mL), H2O (30 mL), and brine (30 mL)
  17. dry with materialThe organic layer was dried over MgSO4
  18. filtrationfiltered
  19. customevaporated
  20. custompurified by flash column chromatography (10% ethyl acetate (EtOAc)/Hexane)
  21. customThe product was further purified
  22. washby washing with cold CH2Cl2

Sources & evidence

ORD record
ord-aaf609bed84248af852bc170c4a40f2d
Source dataset
uspto-grants-1999_01
Patent number
US05856517

Linked notes

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