Pyridine → 3-Chloro-3-(2-ethoxypyridin-3-yl)-2-oxoindoline-5-carbonitrile

HRID 2368450Notes

Reaction equation

HRID 2368450 reaction equation
N1C=CC=CC=1.[C:7]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13](=[O:18])[C:12]2(O)[C:19]1[C:20]([O:25][CH2:26][CH3:27])=[N:21][CH:22]=[CH:23][CH:24]=1)#[N:8].S(Cl)([Cl:31])=O.ClCCl.CO>ClCCl>[Cl:31][C:12]1([C:19]2[C:20]([O:25][CH2:26][CH3:27])=[N:21][CH:22]=[CH:23][CH:24]=2)[C:11]2[C:15](=[CH:16][CH:17]=[C:9]([C:7]#[N:8])[CH:10]=2)[NH:14][C:13]1=[O:18]

Participants

6

Reactant 4

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 21226129Dichloromethane methanolHCID 670486385-Cyano-3-hydroxy-3-(2-ethoxypyridin-3-yl)-1,3-dihydroindol-2-one

Product 1

HCID 670485043-Chloro-3-(2-ethoxypyridin-3-yl)-2-oxoindoline-5-carbonitrileYield 89.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2.30 ml (28.45 mmol) of pyridine were added to a suspension of 6.00 g (20.32 mmol) of 5-cyano-3-hydroxy-3-(2-ethoxypyridin-3-yl)-1,3-dihydroindol-2-one from example 1.2 in 60 ml of anhydrous dichloromethane (dried over molecular sieves) under nitrogen. After the reaction mixture had been cooled to 0° C., 2.06 ml (28.45 mmol) of thionyl chloride, undiluted, were added dropwise (exothermic reaction), and the reaction mixture was then stirred at room temperature for one hour. A yellow suspension formed. The progress of the reaction was followed by thin-layer chromatography (TLC) (silica gel, dichloromethane/methanol in the ratio 95:5). The reaction mixture was cautiously poured into ice-water. After stirring for 15 minutes, the organic phase was separated off. The aqueous phase was extracted with dichloromethane (2×). All the organic phases were combined and dried over magnesium sulfate and filtered, and the solvent was removed in vacuo. 5.70 g (18.17 mmol, 89%) of the title compound were obtained as an amorphous solid which was employed without further purification in the next stage.

Workup

  1. custom(exothermic reaction)
  2. customA yellow suspension formed
  3. stirringAfter stirring for 15 minutes
  4. customthe organic phase was separated off
  5. extractionThe aqueous phase was extracted with dichloromethane (2×)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-de785ee0f9354cdf876f143a43faeb64
Source dataset
uspto-grants-2014_04
Patent number
US08703775B2

Reaction notes

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