1,2-Dichloroethane → (R,E)-3-(1H-indol-3-yl)-N-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethyl)acrylamide

HRID 511861

Reaction equation

HRID 511861 reaction equation
Cl.Cl.[F:3][C:4]([F:17])([F:16])[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([C@H:13]([NH2:15])[CH3:14])=[N:11][CH:12]=1.C([N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])C.[CH2:25](Cl)[CH2:26]Cl.C1C=[CH:31][C:32]2N(O)N=N[C:33]=2[CH:34]=1.[C:39](=[O:42])(O)[O-].[Na+]>ClCCl>[NH:20]1[C:21]2[C:22](=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:24](/[CH:25]=[CH:26]/[C:39]([NH:15][C@@H:13]([C:10]2[CH:9]=[CH:8][C:7]([O:6][CH2:5][C:4]([F:3])([F:16])[F:17])=[CH:12][N:11]=2)[CH3:14])=[O:42])=[CH:23]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 66892447(1R)-1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethan-1-amine dihydrochloride

Product 1

HCID 67290429(R,E)-3-(1H-indol-3-yl)-N-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethyl)acrylamideYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of (R)-1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethanamine 2HCl salt (1.1 g, 3.8 mmol) and (E)-3-(1-(tert-butoxycarbonyl)-1H-indol-3-yDacrylic acid (1.0 g, 3.5 mmol) in dichloromethane (8 mL) were added triethylamine (1.8 g, 17 mmol), EDC (800 mg, 4.2 mmol) and HOBT (270 mg, 1.7 mmol) respectively. The reaction mixture was stirred at room temperature for 6 hours. Sat. sodium bicarbonate aqueous solution was added to the mixture. The organic layer was extracted with ethyl acetate, washed with brine, and dried over sodium sulfate. After the filtration to separate solvent and sodium sulfate, the solvent was removed under reduced pressure to give the residue, which was applied to a silica gel chromatography column and eluted with a hexane/ethylacetate=2/1 (v/v) to furnish 900 mg (53% yield) of the title as a yellow solid;

Workup

  1. extractionThe organic layer was extracted with ethyl acetate
  2. washwashed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationAfter the filtration
  5. customto separate solvent and sodium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customto give the residue, which
  8. washeluted with a hexane/ethylacetate=2/1 (v/v)
  9. customto furnish 900 mg (53% yield) of the title as a yellow solid

Sources & evidence

ORD record
ord-cfa6a7c8a0014b629927e1d38570f8d8
Source dataset
uspto-grants-2015_08
Patent number
US09101616B2

Linked notes

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