Reaktion #472852

Reaktionsgleichung

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

sodium hydrogen carbonate

→

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

Ausbeute 14.2%

Lösungsmittel

methanol

acetic acid

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwere added at room temperature
2. 2
   Sonstigethe organic layer was separated
3. 3
   Extraktionthe aqueous layer was extracted with ethyl acetate
4. 4
   Waschenthe resultant solution was washed with a saturated aqueous sodium chloride solution
5. 5
   Trocknendried over anhydrous magnesium sulfate
6. 6
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
7. 7
   SonstigeThe resultant residue was purified by basic silica gel column chromatography

Vorschrift

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 3 A, 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.

Quelle