反応 #169096

反応方程式

chloroacetyl chloride

Chloroacetyl chloride

7-bromo-N4-(tetrahydro-2H-pyran-4-ylmethyl)quinoline-3,4-diamine

→

N-{7-bromo-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]quinolin-3-yl}-2-chloroacetamide

収率 44.1%

溶媒

dichloromethane

dichloromethane

反応条件

後処理

1. 1
   その他A solid formed
2. 2
   workup.ADDITIONwas added
3. 3
   その他The yellow suspension was quenched first with aqueous saturated sodium bicarbonate
4. 4
   ろ過Filtration

実験手順

Chloroacetyl chloride (5.2 mL, 65 mmol) was added to 7-bromo-N4-(tetrahydro-2H-pyran-4-ylmethyl)quinoline-3,4-diamine (55 mmol) dissolved in 273 mL of dichloromethane at 0° C. A solid formed after adding half of the chloroacetyl chloride at which point additional dichloromethane (100 mL) was added. The reaction was stirred for 1 hour at ambient temperature. The yellow suspension was quenched first with aqueous saturated sodium bicarbonate followed by 50% aqueous sodium hydroxide until a pH of 14 was reached. Filtration provided 10 g of N-{7-bromo-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]quinolin-3-yl}-2-chloroacetamide as a tan solid. The filtrate was placed in a separatory funnel and the layers were separated. The aqueous layer was extracted with additional dichloromethane. The combined organic extracts were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford additional N-{7-bromo-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]quinolin-3-yl}-2-chloroacetamide as a yellow oil. The yellow oil was carried forward without further purification assuming a 50% yield (27.3 mmol). The oil was combined with ethanol (100 mL) and triethylamine (7.5 mL, 54 mmol). The resulting yellow solution was refluxed for 2 hours. The reaction was cooled to ambient temperature and the solvent was removed under reduced pressure to provide 7-bromo-2-(chloromethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinoline as a brown oil that was used without further purification assuming quantitative yield.

出典