Sodium Bicarbonate → 1-Acetyl-2,3-dihydro-5-[2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]-1H-indole-7-carbonitrile

HRID 273854Notes

Reaction equation

HRID 273854 reaction equation
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([CH2:15][CH:16]([NH2:18])[CH3:17])=[CH:10][C:11]=2[C:13]#[N:14])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].Br[CH2:20][CH2:21][O:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[O:29][CH2:30][C:31]([F:34])([F:33])[F:32].C(=O)(O)[O-].[Na+]>C(O)C>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([CH2:15][CH:16]([NH:18][CH2:20][CH2:21][O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[O:29][CH2:30][C:31]([F:32])([F:33])[F:34])[CH3:17])=[CH:10][C:11]=2[C:13]#[N:14])[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 200943331-Acetyl-5-(2-aminopropyl)-2,3-dihydro-1H-indole-7-carbonitrileHCID 200943351-(2-Bromoethoxy)-2-(2,2,2-trifluoroethoxy)benzene

Product 1

HCID 200943401-Acetyl-2,3-dihydro-5-[2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]-1H-indole-7-carbonitrileYield 56.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 1-acetyl-5-(2-aminopropyl)indoline-7-carbonitrile (1.37 g) and 1-(2-bromoethoxy)-2-(2,2,2-trifluoroethoxy)benzene (1.50 g) in ethanol (6 ml) was added sodium bicarbonate (0.47 g), and the mixture was reacted in a sealed tube at 95° C. for 12 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by medium pressure liquid column chromatography on silica gel using a mixture of methylene chloride, diethyl ether and methanol (5/5/1) as eluent, and recrystallized from diethyl ether-hexane to give 1.30 g of 1-acetyl-5-[2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino]propyl]indoline-7-carbonitrile melting at 64°-65° C.

Workup

  1. customthe mixture was reacted in a sealed tube at 95° C. for 12 hours
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthe residue was purified by medium pressure liquid column chromatography on silica gel using
  4. additiona mixture of methylene chloride, diethyl ether and methanol (5/5/1) as eluent
  5. customrecrystallized from diethyl ether-hexane

Sources & evidence

ORD record
ord-1cee60b0311d4c5f8ca5695401856b11
Source dataset
uspto-grants-1995_02
Patent number
US05387603

Reaction notes

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