Reaction #155330

Reaction equation

[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]acetic acid

4-(2-aminoethyl)morpholine

triethylamine

diethylphosphorocyanidate

→

2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]-N-(2-morpholin-4-ylethyl)acetamide

Yield 77.0%

Solvents

Water

DMF

DMF

DMF

Conditions

Workup

1. 1
   Temperaturecooling
2. 2
   Extractionsubjected to extraction
3. 3
   WashThe thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution twice
4. 4
   Dryingdried over anhydrous sodium sulfate
5. 5
   Concentrationconcentrated under reduced pressure
6. 6
   OtherThe residue was purified
7. 7
   ConcentrationThe purified product was concentrated under reduced pressure
8. 8
   Otherthe residue was recrystallized from ethyl acetate

Procedure

To a DMF solution (2 ml) of [5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]acetic acid (800 mg, 2.07 mmol) were sequentially added a DMF solution (1 ml) of 4-(2-aminoethyl)morpholine (273 mg), triethylamine (506 mg, 5.0 mmol), diethylphosphorocyanidate (DEPC, 405 mg, 2.48 mmol) and DMF (1 ml) while ice-cooling, followed by stirring at room temperature for 23 hours. Water was added to the reaction mixture and then subjected to extraction using ethyl acetate. The thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution twice, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified using silica gel column chromatography (dichloromethane:methanol=30:1→15:1). The purified product was concentrated under reduced pressure, and the residue was recrystallized from ethyl acetate, giving a white powder of 2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]-N-(2-morpholin-4-ylethyl)acetamide (789 mg, yield: 77%).

Source