Triethylamine → 3-{1-[1-(2,2,3,3,4,4,4-Heptafluoro-butyl)-piperidin-4-yl]-indol-3-yl}-4-(1-methyl-indol-3-yl)-1H-pyrrole-2,5-dione

HRID 1379751Notes

Reaction equation

HRID 1379751 reaction equation
[F:1][C:2]([F:26])([F:25])[C:3]([F:24])([F:23])[C:4]([F:22])([F:21])[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH:14]=[CH:13]2)[CH2:8][CH2:7]1.[C:27](Cl)(=[O:31])[C:28](Cl)=O.Cl.[C:34](=[NH:37])([OH:36])[CH3:35].[CH2:38]([N:40]([CH2:43][CH3:44])[CH2:41][CH3:42])C.O.[C:46]1(C)[CH:51]=CC(S(O)(=O)=O)=[CH:48][CH:47]=1>CCOCC.C(Cl)Cl>[F:22][C:4]([F:21])([C:3]([F:23])([F:24])[C:2]([F:1])([F:25])[F:26])[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]([C:35]3[C:34](=[O:36])[NH:37][C:27](=[O:31])[C:28]=3[C:42]3[C:44]4[C:43](=[CH:51][CH:46]=[CH:47][CH:48]=4)[N:40]([CH3:38])[CH:41]=3)=[CH:13]2)[CH2:8][CH2:7]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 521998p-Toluenesulfonic acid monohydrateHCID 229072781-(4,4,4,3,3,2,2-Heptafluorobutyl)-4-(1-indolyl)-piperidineHCID 178465697HCID 178465697, compound

Product 1

HCID 229072823-{1-[1-(2,2,3,3,4,4,4-Heptafluoro-butyl)-piperidin-4-yl]-indol-3-yl}-4-(1-methyl-indol-3-yl)-1H-pyrrole-2,5-dione

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred 0° C. solution of 1-(4,4,4,3,3,2,2-heptafluorobutyl)-4-(1-indolyl)-piperidine (430 mg, 1.12 mmol) in dry ether (5 mL) was added oxalyl chloride (0.11 mL, 1.23 mmol). After 1 hour at room temperature, a yellow precipitate formed. The precipitant was collected by filtration under Ar, washed with ether, suspended in dry methylene chloride (10 mL) and treated with isopropyl(1-methyl)indol-3-yl)acetimidate hydrochloride (300 mg, 1.12 mmol). To this suspension was added triethylamine (0.78 mL, 5.6 mmol) in dry methylene chloride (3 mL) at 0° C. The reaction was stirred at ambient temperature for 3 hours and treated with p-toluene sulfonic acid monohydrate (slightly exothermic) (0.86 g, 4.5 mmol). After 30 minutes, the reaction was carefully quenched with saturated aqueous sodium hydrogen carbonate solution (30 mL). The organic phase was separated, washed with saturated aqueous sodium hydrogen carbonate solution, water, brine, dried, and evaporated. The residue was crystallized from an ethereal solution. Yield: 260 mg of bright orange crystals (38% of theory). M.Pt.: 231°-234° C.

Workup

  1. customa yellow precipitate formed
  2. filtrationThe precipitant was collected by filtration under Ar
  3. washwashed with ether
  4. waitAfter 30 minutes
  5. customthe reaction was carefully quenched with saturated aqueous sodium hydrogen carbonate solution (30 mL)
  6. customThe organic phase was separated
  7. washwashed with saturated aqueous sodium hydrogen carbonate solution, water, brine
  8. customdried
  9. customevaporated
  10. customThe residue was crystallized from an ethereal solution

Sources & evidence

ORD record
ord-d5b476800b88450bba4782b6710fe3d2
Source dataset
uspto-grants-1997_09
Patent number
US05672618

Reaction notes

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