Water → Methyl 5-chloro-1-(quinolin-4-yl)-1H-indole-3-carboxylate

HRID 492216Notes

Reaction equation

HRID 492216 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[C:13]([O:15][CH3:16])=[O:14].Cl[C:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[CH:20][CH:19]=1.O>CN(C)C=O>[Cl:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([C:18]1[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=[CH:20][CH:19]=1)[CH:8]=[C:7]2[C:13]([O:15][CH3:16])=[O:14]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 691404-ChloroquinolineHCID 15859771Methyl 5-chloro-1H-indole-3-carboxylate

Product 1

HCID 68968651Methyl 5-chloro-1-(quinolin-4-yl)-1H-indole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

0.771 g (24 mmol) of sodium hydride at 75% by weight in liquid petroleum jelly is added to a solution of 5.03 g (24 mmol) of 5-chloro-3-methoxycarbonyl-1H-indole in 120 cm3 of dimethylformamide at a temperature in the region of 20° C. under an argon atmosphere. After the reaction mixture has been stirred for 0.5 hour at a temperature in the region of 40° C., 3.94 g (24 mmol) of 4-chloroquinoline are added. After stirring for 6 hours at a temperature in the region of 120° C., the reaction mixture is cooled to a temperature in the region of 20° C. and then poured into 400 cm3 of water and extracted with 500 cm3 of ethyl acetate. The organic phase is washed three times with 250 cm3 of water, dried over anhydrous magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa). The residue is purified by chromatography on silica gel (eluent: dichloromethane). After the fractions containing the expected product have been concentrated to dryness under reduced pressure, 2.5 g of 5-chloro-3-methoxycarbonyl-1-(quinolin-4-yl)-1H-indole are obtained in the form of a sticky beige-colored solid, which is used in the following step without further purification.

Workup

  1. additionare added
  2. temperaturethe reaction mixture is cooled to a temperature in the region of 20° C.
  3. extractionextracted with 500 cm3 of ethyl acetate
  4. washThe organic phase is washed three times with 250 cm3 of water
  5. dry with materialdried over anhydrous magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  8. customThe residue is purified by chromatography on silica gel (eluent: dichloromethane)
  9. additionAfter the fractions containing the expected product
  10. concentrationhave been concentrated to dryness under reduced pressure, 2.5 g of 5-chloro-3-methoxycarbonyl-1-(quinolin-4-yl)-1H-indole
  11. customare obtained in the form of a sticky beige-colored solid, which
  12. customis used in the following step without further purification

Sources & evidence

ORD record
ord-424da9b834db4b69bbea5e498e06934b
Source dataset
uspto-grants-2009_05
Patent number
US07531663B2

Reaction notes

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