To 3.0 mL of tetrahydrofuran suspension containing 0.15 g of 1-(2-(4-((tert-butoxycarbonyl)(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-methoxy-2-oxo-1,2-dihydroquinoline-4-carboxylic acid, 39 μL of triethylamine was added at room temperature, 36 μL of isobutyl chlorocarbonate was added dropwise under ice-cooling. After the reaction mixture was stirred at the same temperature for 2 hours, 26 μL of 3-(aminomethyl)pyridine was added, further 39 μL of triethylamine was added and stirred at the same temperature for 3 hours. To the reaction mixture, ethyl acetate and water were added, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and extracts were combined, washed sequentially with water and aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by flash silica gel column chromatography [gradient elution of chloroform:methanol=100:0-90:10], to give 0.12 g of tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(7-methoxy-2-oxo-4-(((pyridin-3-ylmethyl)amino)carbonyl)quinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate as a white foam.
