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

HRID 1369101Notes

Reaction equation

HRID 1369101 reaction equation
[CH2:1]([N:3]([CH2:26][CH3:27])[CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[C:10]([Br:16])[CH:11]=[C:12](I)[CH:13]=2)[C:8]([OH:24])([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:23])[C:7]1=[O:25])[CH3:2].[O:28]=[C:29]1[N:33]([CH2:34][C:35]#[CH:36])[CH:32]=[CH:31][O:30]1.CCN(CC)CC.C1(C)C=CC=CC=1>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.[Cu]I.C1COCC1>[CH2:1]([N:3]([CH2:26][CH3:27])[CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[C:10]([Br:16])[CH:11]=[C:12]([C:36]#[C:35][CH2:34][N:33]3[CH:32]=[CH:31][O:30][C:29]3=[O:28])[CH:13]=2)[C:8]([OH:24])([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:23])[C:7]1=[O:25])[CH3:2]

Participants

8

Reactant 4

HCID 1140TolueneHCID 8471TriethylamineHCID 119878593-(2-Oxo-1,3-oxazolin-3-yl)-1-propyneHCID 185186541-(2-Diethylaminoethyl)-3-hydroxy-3-(2-chlorophenyl)-4-bromo-6-iodooxindole

Product 1

HCID 185186621-(2-Diethylaminoethyl)-4-bromo-6-[3-(2-oxo-1,3-oxazolin-3-yl)-1-propynyl]-3-hydroxy-3-(2-chlorophenyl)oxindoleYield 76.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
50 °C

Procedure

To 1-(2-diethylaminoethyl)-3-hydroxy-3-(2-chlorophenyl)-4-bromo-6-iodooxindole (31.5 mg, 5.84×10−5 mol), 3-(2-Oxo-1,3-oxazolin-3-yl)-1-propyne (10.95 mg, 1.5 eq.), Pd(PPh3)2Cl2 (6.15 mg, 15 mol %) and CuI (1.7 mg, 15 mol %) under a nitrogen atmosphere was added anhydrous Et3N (0.5 mL), anhydrous toluene (0.5 mL) and anhydrous THF (0.5 mL). The resulting yellow mixture was heated to 50° C. (bath temperature) and stirred at that temperature for 1 hour and 20 minutes. The solvent was then removed in vacuo to give a yellow solid. Purification was carried out by column chromatography (silica gel, 3% MeOH in CHCl3) to yield the title compound (24.9 mg, 76%) as a white solid. The hydrochloride of the title compound was obtained by treating with 4 N HCl in dioxane followed by concentration to dryness.

Workup

  1. customThe solvent was then removed in vacuo
  2. customto give a yellow solid
  3. customPurification

Sources & evidence

ORD record
ord-1b9e76b96a894e058397094a5fdfa1e8
Source dataset
uspto-grants-2003_06
Patent number
US06576656B1

Reaction notes

Loading…