反応 #1597962

反応方程式

(3S)—N-(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)pyrrolidin-3-amine hydrochloride

sodium methoxide methanol

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

sodium cyanoborohydride

sodium hydrogen carbonate

→

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

収率 39.8%

溶媒

methanol

acetic acid

ethyl acetate

反応条件

後処理

1. 1
   その他the organic layer was separated
2. 2
   抽出the aqueous layer was extracted with ethyl acetate
3. 3
   洗浄the resultant solution was washed with a saturated aqueous sodium chloride solution
4. 4
   乾燥dried over anhydrous magnesium sulfate
5. 5
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
6. 6
   その他The resultant residue was purified by basic silica gel column chromatography
7. 7
   workup.ADDITIONmethanol=30:1, thereto were added ethyl acetate
8. 8
   ろ過a 4 mol/L hydrogen chloride/ethyl acetate solution, and the solid was filtered off

実験手順

To a solution of 62 mg of (3S)—N-(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)pyrrolidin-3-amine hydrochloride in 3 mL of methanol, 0.10 g of a 28% sodium methoxide/methanol solution, 37 mg of (7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde, 60 μL of acetic acid, 0.12 g of molecular sieves 3A and 11 mg of sodium cyanoborohydride were added at room temperature, and the mixture was stirred at the same temperature for 1 hour 10 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, thereto were added ethyl acetate and a 4 mol/L hydrogen chloride/ethyl acetate solution, and the solid was filtered off to obtain 33 mg of 1-(2-((3S)-3-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)pyrrolidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one hydrochloride as a yellow solid.

出典