Water → 1-(2-Diethylaminoethyl)-4-trifluoromethyl-6-[3-(2-oxo-1,3-oxazolin-3-yl)-1-propynyl]-3-hydroxy-3-(2-chlorophenyl)oxindole

HRID 1369106Notes

Reaction equation

HRID 1369106 reaction equation
[CH2:1]([N:3]([CH2:29][CH3:30])[CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[C:10]([C:16]([F:19])([F:18])[F:17])[CH:11]=[C:12](I)[CH:13]=2)[C:8]([OH:27])([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[Cl:26])[C:7]1=[O:28])[CH3:2].[O:31]=[C:32]1[N:36]([CH2:37][C:38]#[CH:39])[CH:35]=[CH:34][O:33]1.O.C([O-])(O)=O.[Na+]>C(N(CC)CC)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([N:3]([CH2:29][CH3:30])[CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[C:10]([C:16]([F:19])([F:18])[F:17])[CH:11]=[C:12]([C:39]#[C:38][CH2:37][N:36]3[CH:35]=[CH:34][O:33][C:32]3=[O:31])[CH:13]=2)[C:8]([OH:27])([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[Cl:26])[C:7]1=[O:28])[CH3:2]

Participants

8

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 119878593-(2-Oxo-1,3-oxazolin-3-yl)-1-propyneHCID 129902161-(2-Diethylaminoethyl)-4-trifluoromethyl-6-iodo-3-hydroxy-3-(2-chlorophenyl)oxindole

Product 1

HCID 185185761-(2-Diethylaminoethyl)-4-trifluoromethyl-6-[3-(2-oxo-1,3-oxazolin-3-yl)-1-propynyl]-3-hydroxy-3-(2-chlorophenyl)oxindoleYield 935.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 1-(2-diethylaminoethyl)-4-trifluoromethyl-6-iodo-3-hydroxy-3-(2-chlorophenyl)oxindole (796 mg, 0.144 mmol), 3-(2-oxo-1,3-oxazolin-3-yl)-1-propyne (464 mg, 0.371 mmol), CuI (10.8 mg, 0.0567 mmol), and (PPh3)2PdCl2 (18.6 mg, 0.0265 mmol) in triethylamine (1 mL) was stirred for 4.5 h at 50° C. Water and sat. aqueous NaHCO3 were added and the mixture was extracted with ethyl acetate. The extracts were dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography with 80:1 to 50:1 chloroform/methanol to give the title compound (738 mg). The compound was dissolved in dioxane (2 mL) and 4 N HCl in dioxane (1 mL) was added. The solvent was evaporated azeotropically with toluene. The residual solid was washed with ether and dried in vacuo to give the hydrochloride (528 mg, 63%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialThe extracts were dried over MgSO4
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel column chromatography with 80:1 to 50:1 chloroform/methanol

Sources & evidence

ORD record
ord-9e4def75de134fc79512c931a790fd92
Source dataset
uspto-grants-2003_06
Patent number
US06576656B1

Reaction notes

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