A 2 L round flask, under argon, was charged with a solution of the 14.00 g amine( 6-Amino-4-trifluoromethylquinolin-2(1H)-one )in 350 ml trifluoroacetic acid. 5.80 g NaBH4 was added within 1 h. The mixture was stirred at room temperature for 16 h. After that 4.50 g NaBH4 was added and then heated to 70°C for 5 h. The heating bath was removed and it was stirred at room temperature over 2 d. In several portions water was carefully added. In total 1500 ml water was slowly added. The yellow-greenish precipitate was filtered and rinsed with water. After drying, the crude product was purified by column chromatography on silica gel by using hexane-ethyl acetate (1:4), followed by a recrystallization in chloroform. 18.1 g of LGD-2226 was obtained as a bright yellow solid (76%).
