Toluene → N5-Allyl-6-chloro-1-methyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide

HRID 339123Notes

Reaction equation

HRID 339123 reaction equation
[CH2:1]([NH2:4])[CH:2]=[CH2:3].C[Al](C)C.C1(C)C=CC=CC=1.[Cl:16][C:17]1[CH:25]=[C:24]2[C:20]([CH:21]=[C:22]([C:27](=[O:44])[NH:28][CH:29]([C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=3)[C:30]([F:33])([F:32])[F:31])[N:23]2[CH3:26])=[CH:19][C:18]=1[C:45](OCC)=[O:46]>ClCCl.O>[CH2:1]([NH:4][C:45]([C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][C:17]=1[Cl:16])[N:23]([CH3:26])[C:22]([C:27]([NH:28][CH:29]([C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:42])([F:43])[F:41])[CH:35]=1)[C:30]([F:31])([F:32])[F:33])=[O:44])=[CH:21]2)=[O:46])[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 1140TolueneHCID 7853AllylamineHCID 16682925TrimethylaluminumHCID 58247953Ethyl 6-chloro-1-methyl-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indole-5-carboxylate

Product 1

HCID 58247974N5-Allyl-6-chloro-1-methyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

Allylamine (156 mg, 2.73 mmol) was dissolved in 3 ml of dichloromethane and admixed dropwise under argon with a solution of trimethylaluminium in toluene (2 M, 1.37 ml, 2.73 mmol). The mixture was stirred for 30 min, and then ethyl 6-chloro-1-methyl-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indole-5-carboxylate (165 mg, 0.27 mmol) dissolved in 3 ml of dichloromethane was added dropwise. The mixture was heated under reflux overnight and, after cooling to room temperature, water was added cautiously. The mixture was extracted with ethyl acetate, the organic phase washed with potassium sodium tartrate solution, dried over magnesium sulphate and filtered, and the filtrate concentrated under reduced pressure. The purification was effected by means of silica gel chromatography with the eluent cyclohexane/ethyl acetate (EA) (0% EA to 30% EA).

Workup

  1. additionwas added dropwise
  2. temperatureThe mixture was heated
  3. temperatureunder reflux overnight
  4. extractionThe mixture was extracted with ethyl acetate
  5. washthe organic phase washed with potassium sodium tartrate solution
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated under reduced pressure
  9. customThe purification

Sources & evidence

ORD record
ord-65d10d6eb81c43edb7986916d00b99ac
Source dataset
uspto-grants-2014_11
Patent number
US08889878B2

Reaction notes

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