2,6-Lutidine → 3-(4-Cyclohexyl-1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)propanoic acid

HRID 1582995Notes

Reaction equation

HRID 1582995 reaction equation
C1COCC1.[CH:6]1([C:12]([C:14]2[C:15]([NH:21][CH2:22][CH3:23])=[N:16][C:17]([CH3:20])=[CH:18][CH:19]=2)=O)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.Cl[CH:25]([CH2:31][CH2:32][C:33]([O-:35])=O)[C:26]([O:28]CC)=[O:27].N1C(C)=CC=CC=1C>O>[CH:6]1([C:12]2[C:14]3[C:15](=[N:16][C:17]([CH3:20])=[CH:18][CH:19]=3)[N:21]([CH2:22][CH3:23])[C:33](=[O:35])[C:32]=2[CH2:31][CH2:25][C:26]([OH:28])=[O:27])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]1

Participants

6

Reactant 4

HCID 79372,6-LutidineHCID 8028TetrahydrofuranHCID 227166563-Cyclohexanecarbonyl-2-ethylamino-6-methylpyridineHCID 22716689Monoethyl chloroglutarate

Product 1

HCID 227166603-(4-Cyclohexyl-1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)propanoic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a 20 ml THF solution containing 2.34 g of 3-cyclohexanecarbonyl-2-ethylamino-6-methylpyridine were added 3 ml of monoethyl chloroglutarate and 2.8 ml of 2,6-lutidine, followed by stirring under heating at an oil bath temperature of 60° C. for 1 hour. After the reaction mixture was cooled to room temperature, water was added thereto, and the whole was extracted with ethyl acetate. The organic layer was washed with 3M hydrochloric acid, saturated sodium bicarbonate aqueous solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated and 1.00 g of sodium methoxide was added to a 20 ml ethanol solution of the resulting residue, followed by heating under reflux for 1 hour. Then, 20 ml of a 1M sodium hydroxide aqueous solution was added to the reaction solution, followed by heating under reflex for another 1 hour. After the mixture was cooled to room temperature, water was added thereto, and the mixture was neutralized with 1M hydrochloric acid and then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was recrystallized from ethanol-water to obtain 764 mg of 3-(4-cyclohexyl-1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)propanoic acid as colorless crystals.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. extractionthe whole was extracted with ethyl acetate
  3. washThe organic layer was washed with 3M hydrochloric acid, saturated sodium bicarbonate aqueous solution and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated
  6. addition1.00 g of sodium methoxide was added to a 20 ml ethanol solution of the resulting residue
  7. temperatureby heating
  8. temperatureunder reflux for 1 hour
  9. additionThen, 20 ml of a 1M sodium hydroxide aqueous solution was added to the reaction solution
  10. temperatureby heating under reflex for another 1 hour
  11. temperatureAfter the mixture was cooled to room temperature
  12. additionwater was added
  13. extractionextracted with ethyl acetate
  14. washThe organic layer was washed with saturated brine
  15. dry with materialdried over anhydrous magnesium sulfate
  16. customThe solvent was evaporated
  17. customthe residue was recrystallized from ethanol-water

Sources & evidence

ORD record
ord-c9289e41664e48208776b4f927d7d47d
Source dataset
uspto-grants-2004_05
Patent number
US06740662B1

Reaction notes

Loading…