Reaktion #155336

Reaktionsgleichung

1-(2-Methoxyethyl)piperazine

triethylamine

2-Chloro-N-{3-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]propyl}acetamide

→

N-{3-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]propyl}-2-[4-(2-methoxyethyl)piperazin-1-yl]acetamide hydrochloride

Ausbeute 41.3%

Lösungsmittel

acetonitrile

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe resulting mixture was concentrated under reduced pressure
2. 2
   Extraktionthe residue was subjected to extraction
3. 3
   WaschenThe extract was then sequentially washed with water
4. 4
   EinengenThe washed product was concentrated under reduced pressure
5. 5
   Sonstigethe residue was purified
6. 6
   EinengenThe purified product was concentrated under reduced pressure
7. 7
   workup.DISSOLUTIONthe residue was then dissolved in ethyl acetate (5 ml)
8. 8
   workup.ADDITIONA 4N hydrogen chloride ethyl acetate solution (0.19 ml) was added
9. 9
   workup.STIRRINGstirred
10. 10
    Einengenthe mixture was concentrated to dryness under reduced pressure

Vorschrift

2-Chloro-N-{3-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]propyl}acetamide (370 mg, 0.8 mmol) was suspended in acetonitrile (12 ml). 1-(2-Methoxyethyl)piperazine (138 mg, 0.96 mmol), triethylamine (162 mg, 1.6 mmol) and acetonitrile (2 ml) were added to the suspension, and stirred at 70 to 80° C. for 6 hours. The resulting mixture was concentrated under reduced pressure, and the residue was subjected to extraction using ethyl acetate. The extract was then sequentially washed with water, an aqueous saturated sodium chloride solution, and an aqueous saturated sodium bicarbonate solution. The washed product was concentrated under reduced pressure, and the residue was purified using silica gel column chromatography (dichloromethane:methanol=30:1→10:1). The purified product was concentrated under reduced pressure, and the residue was then dissolved in ethyl acetate (5 ml). A 4N hydrogen chloride ethyl acetate solution (0.19 ml) was added thereto and stirred, and then the mixture was concentrated to dryness under reduced pressure, giving a pale yellow amorphous solid of N-{3-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]propyl}-2-[4-(2-methoxyethyl)piperazin-1-yl]acetamide hydrochloride (200 mg).

Quelle