Triethylamine → 3-(1-Methyl-indol-3-yl)-4-{1-[1-{2,2,2-trifluoro-ethyl)-piperidin-4-yl]-indol-3-yl}-1H-pyrrole-2,5-dione

HRID 1077950Notes

Reaction equation

HRID 1077950 reaction equation
[F:1][C:2]([F:20])([F:19])[CH2:3][N:4]1[CH2:9][CH2:8][CH:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[CH:11]2)[CH2:6][CH2:5]1.[C:21](Cl)(=[O:25])[C:22](Cl)=O.Cl.[C:28](=[NH:31])([OH:30])[CH3:29].[CH2:32]([N:34]([CH2:37][CH3:38])[CH2:35][CH3:36])C.O.[C:40]1(C)[CH:45]=CC(S(O)(=O)=O)=[CH:42][CH:41]=1>CCOCC>[CH3:32][N:34]1[C:37]2[C:38](=[CH:45][CH:40]=[CH:41][CH:42]=2)[C:36]([C:29]2[C:28](=[O:30])[NH:31][C:21](=[O:25])[C:22]=2[C:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:10]([CH:7]3[CH2:8][CH2:9][N:4]([CH2:3][C:2]([F:1])([F:19])[F:20])[CH2:5][CH2:6]3)[CH:11]=2)=[CH:35]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 65578Oxalyl chloride2×HCID 521998p-Toluenesulfonic acid monohydrateHCID 229072831-[1-(2,2,2-Trifluoroethyl)-piperidin-4-yl]-indoleHCID 178465697HCID 178465697, compound

Product 1

HCID 229072483-(1-Methyl-indol-3-yl)-4-{1-[1-{2,2,2-trifluoro-ethyl)-piperidin-4-yl]-indol-3-yl}-1H-pyrrole-2,5-dioneYield 30.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a stirred 0° C. solution of 1-[1-(2,2,2-trifluoro-ethyl)-piperidin-4-yl]-indole (180 mg, 0.64 mmol) in dry ether (3 mL ) was added oxalyl chloride (0.06 mL, 0.7 mmol). The reaction mixture was warmed to ambient temperature for 30 minutes. An additional amount of oxalyl chloride (0.04 mL, 0.5 mmol ) was added. After 30 minutes, a yellow precipitate formed which was filtered with the exclusion of moisture and air, and washed with a small amount of ether. The collected precipitant was dissolved in dry methylene chloride (10 mL) and treated with isopropyl(1-methyl) indol-3-yl)acetimidate hydrochloride (190 mg, 0.71 mmol ) followed by slow addition of triethylamine (0.44 mL, 3.2 mmol) at 0° C. After 4 hours at ambient temperature, p-toluene sulfonic acid monohydrate (0.61 g, 3.2 mmol) was added. After 30 minutes the mixture was quenched with saturated aqueous sodium hydrogen carbonate solution (40 mL). The organic phase was separated, washed with water, dried, and evaporated. The residue was recrystallized from hot dioxane and yielded 100 mg of bright orange crystals. Recrystallization of the mother liquor from THF yielded a second crop (60 mg). Yield: 160 mg of bright orange crystals (49% of theory) M.Pt.: >250° C.

Workup

  1. customa yellow precipitate formed which
  2. filtrationwas filtered with the exclusion of moisture and air
  3. washwashed with a small amount of ether
  4. dissolutionThe collected precipitant was dissolved in dry methylene chloride (10 mL)
  5. waitAfter 4 hours at ambient temperature
  6. customAfter 30 minutes the mixture was quenched with saturated aqueous sodium hydrogen carbonate solution (40 mL)
  7. customThe organic phase was separated
  8. washwashed with water
  9. customdried
  10. customevaporated
  11. customThe residue was recrystallized from hot dioxane

Sources & evidence

ORD record
ord-3a76e7e19651415b896ca240cdbbacba
Source dataset
uspto-grants-1996_08
Patent number
US05545636

Reaction notes

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