Reaktion #1597962

Reaktionsgleichung

(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

Ausbeute 39.8%

Lösungsmittel

methanol

acetic acid

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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.

Quelle