Triethylamine → 1-(2-Diethylaminoethyl)-4-trifluoromethyl-6-[3-(2-oxo-1-imidazolidinyl)-1-propynyl]-3-hydroxy-3-(2-chlorophenyl)oxindole

HRID 1369104Notes

Reaction equation

HRID 1369104 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[NH:36][CH2:35][CH2:34][N:33]1[CH2:37][C:38]#[CH:39].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>[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.O.C1(C)C=CC=CC=1.C1COCC1>[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:33]3[CH2:34][CH2:35][NH:36][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

10

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 129902161-(2-Diethylaminoethyl)-4-trifluoromethyl-6-iodo-3-hydroxy-3-(2-chlorophenyl)oxindoleHCID 156696571-(Prop-2-yn-1-yl)imidazolidin-2-one

Product 1

HCID 185185741-(2-Diethylaminoethyl)-4-trifluoromethyl-6-[3-(2-oxo-1-imidazolidinyl)-1-propynyl]-3-hydroxy-3-(2-chlorophenyl)oxindoleYield 875.7%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 1-(2-diethylaminoethyl)-4-trifluoromethyl-6-iodo-3-hydroxy-3-(2-chlorophenyl)oxindole (720 mg, 0.13 mmol), 3-(2-oxo-1-imidazolidinyl)-1-propyne (280 mg, 0.226 mmol), triethylamine (1 mL), CuI (12.8 mg, 0.0372 mmol), and (PPh3)2PdCl2 (22.6 mg, 0.0322 mmol) in a mixed solvent of THF (0.5 mL) and toluene (0.5 mL) was stirred for 3 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 30:1 to 20:1 chloroform/methanol to give the title compound (625 mg). The compound was dissolved in dioxane (4 mL) and 4 N HCl in dioxane (1.5 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 (583 mg, 77%).

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 30:1 to 20:1 chloroform/methanol

Sources & evidence

ORD record
ord-48c3ad75a71c4d7eb2fddead72259171
Source dataset
uspto-grants-2003_06
Patent number
US06576656B1

Reaction notes

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