p-Toluenesulfonic acid → 3-[1-(1-Methyl-piperidin-4-yl)-indol-3-yl]-4-(1-methyl-indol-3-yl)-1H-pyrrole-2,5-dione

HRID 1077948Notes

Reaction equation

HRID 1077948 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]=[CH:9]2)[CH2:4][CH2:3]1.[C:17](Cl)(=[O:21])[C:18](Cl)=O.Cl.[C:24](=[NH:27])([OH:26])[CH3:25].[CH2:28]([N:30]([CH2:33][CH3:34])[CH2:31][CH3:32])C.[C:35]1(C)[CH:40]=CC(S(O)(=O)=O)=[CH:37][CH:36]=1.C(=O)([O-])O.[Na+]>CCOCC>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([C:25]3[C:24](=[O:26])[NH:27][C:17](=[O:21])[C:18]=3[C:32]3[C:34]4[C:33](=[CH:40][CH:35]=[CH:36][CH:37]=4)[N:30]([CH3:28])[CH:31]=3)=[CH:9]2)[CH2:4][CH2:3]1

Participants

8

Reactant 6

HCID 6101p-Toluenesulfonic acidHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 140907431-(1-methyl-piperidin-4-yl)-1H-indoleHCID 178465697HCID 178465697, compound

Product 1

HCID 98893513-[1-(1-Methyl-piperidin-4-yl)-indol-3-yl]-4-(1-methyl-indol-3-yl)-1H-pyrrole-2,5-dioneYield 41.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To an ice cooled solution of 1-(1-methyl-piperidin-4-yl)-1H-indole (38 g, 0.177 mol) in dry ether (1.2 L) was added oxalyl chloride (16.7 mL, 0.195 mol) dropwise at a rate such that the internal temperature does not exceed 5° C. Stirring at 0° to 5° C. is continued for 30 minutes. A yellow precipitate was isolated by suction filtration, washed with ether (800 mL) and suspended in methylene chloride (1.5 L). The solution was recooled to 0° to 5° C. and treated with isopropyl(1-methyl)indol-3-yl)acetimidate hydrochloride (49.6 g, 0.186 mol) in one portion followed by dropwise addition of triethylamine (123 mL, 0.885 mol). The reaction was brought to ambient temperature and stirred for 3 hours. Anhydrous p-toluene sulfonic acid (152.4 g) was added in several portions with external cooling and stirring was continued for 30 minutes. The mixture was poured into saturated aqueous sodium hydrogen carbonate (2 L) and shaken. A bright orange precipitate (32.2 g) formed which was isolated by suction filtration and washed successively with water, dioxane, and ether. A second crop was isolated by evaporation of the mother liquor and trituration with dioxane (9.4 g). Total yield: 41.6 g (54% of theory). M.Pt.: 316°-318° C.

Workup

  1. customdoes not exceed 5° C
  2. customA yellow precipitate was isolated by suction filtration
  3. washwashed with ether (800 mL)
  4. customwas recooled to 0° to 5° C.
  5. customwas brought to ambient temperature
  6. stirringstirred for 3 hours
  7. temperaturewith external cooling
  8. stirringstirring
  9. waitwas continued for 30 minutes
  10. stirringshaken

Sources & evidence

ORD record
ord-d76eceb65cc44bc4b4a24411f74535f8
Source dataset
uspto-grants-1996_08
Patent number
US05545636

Reaction notes

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