反応 #1597965

反応方程式

sodium hydrogen carbonate

1-(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-yl)-N-(pyrrolidin-3-ylmethyl)methanamine hydrochloride

sodium methoxide methanol

(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde

sodium cyanoborohydride

→

1-(2-(3-(((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)methyl)pyrrolidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one

収率 14.2%

溶媒

ethyl acetate

methanol

acetic acid

反応条件

後処理

1. 1
   workup.ADDITIONwere added at room temperature
2. 2
   その他the organic layer was separated
3. 3
   抽出the aqueous layer was extracted with ethyl acetate
4. 4
   洗浄the resultant solution was washed with a saturated aqueous sodium chloride solution
5. 5
   乾燥dried over anhydrous magnesium sulfate
6. 6
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
7. 7
   その他The resultant residue was purified by basic silica gel column chromatography

実験手順

To a suspension of 0.10 g of 1-(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-yl)-N-(pyrrolidin-3-ylmethyl)methanamine hydrochloride in 5 mL of methanol, 0.17 g of a 28% sodium methoxide/methanol solution, 66 mg of (7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde, 0.10 g of molecular sieves 3A, 33 μL of acetic acid and 18 mg of sodium cyanoborohydride were added at room temperature, and the mixture was stirred at the same temperature for 2 hours 30 minutes. To the reaction mixture, a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate were added, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by basic silica gel column chromatography using an eluent of chloroform:methanol=30:1 to obtain 20 mg of 1-(2-(3-(((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)methyl)pyrrolidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one as a yellow oily substance.

出典