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

HRID 535880Notes

Reaction equation

HRID 535880 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[C:6]2(O)[C:13]1[C:14]([O:19][CH2:20][CH3:21])=[N:15][CH:16]=[CH:17][CH:18]=1)#[N:2].N1C=CC=CC=1.S(Cl)([Cl:31])=O.ClCCl.CO>ClCCl>[Cl:31][C:6]1([C:13]2[C:14]([O:19][CH2:20][CH3:21])=[N:15][CH:16]=[CH:17][CH:18]=2)[C:5]2[C:9](=[CH:10][CH:11]=[C:3]([C:1]#[N:2])[CH:4]=2)[NH:8][C:7]1=[O:12]

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

Procedure

Under an atmosphere of nitrogen, 6.00 g (20.32 mmol) of the 5-cyano-3-hydroxy-3-(2-ethoxypyridin-3-yl)-1,3-dihydroindol-2-one were suspended in 60 ml of anhydrous dichloromethane (dried over molecular sieve). 2.30 ml (28.45 mmol) of pyridine were then added. The reaction mixture was cooled to a temperature of 0° C., and 2.06 ml (28.45 mmol) of neat thionyl chloride were then added dropwise (exothermic reaction). The mixture was stirred at room temperature for one hour. The formation of a yellow suspension was observed. The course of the reaction was monitored by thin-layer chromatography (TLC) (silica gel, dichloromethane/methanol in a ratio of 95:5). The reaction mixture was carefully poured into ice-water. After 15 minutes of stirring, the organic phase was removed. The aqueous phase was extracted with dichloromethane (2×). All organic phases were combined, dried over magnesium sulphate and filtered, and the solvent was removed under reduced pressure. The product gave 5.70 g (18.17 mmol, 89%) of 3-chloro-3-(2-ethoxypyridin-3-yl)-2-oxoindoline-5-carbonitrile as an amorphous solid which was used without further purification for the next reaction.

Workup

  1. additionwere then added dropwise
  2. custom(exothermic reaction)
  3. stirringAfter 15 minutes of stirring
  4. customthe organic phase was removed
  5. extractionThe aqueous phase was extracted with dichloromethane (2×)
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-8a306e69c6f146a492a28d58e4d7ec97
Source dataset
uspto-grants-2014_10
Patent number
US08859557B2

Reaction notes

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