反应详情

To (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.2 g, 0.873 mmol) in N,N-dimethylformamide (20 mL) was added Cs2CO3 (0.711 g, 2.182 mmol) and 3-isothiocyanatoisoquinoline (0.163 g, 0.873 mmol). The suspension was stirred at room temperature for 30 minutes. N,N′-Diisopropylcarbodiimide (0.408 mL, 2.62 mmol) was then added and the mixture was stirred at room temperature for 18 hours. The mixture was concentrated and purified by silica gel chromatography (5-25% [9:1 methanol:ammonium hydroxide]-ethyl acetate) to afford (R)—N-(isoquinolin-3-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (0.16 g, 0.508 mmol, 58% yield) as an off-white solid. M.P. 196-200° C. 1H NMR (400 MHz, MeOD) δ ppm 9.00 (1H, s), 7.92 (1H, d), 7.71 (1H, d), 7.59 (1H, t), 7.20-7.45 (2H, m), 3.96 (1H, d), 3.65 (1H, d), 3.22 (1H, d), 3.08 (1H, d), 2.66-3.00 (4H, m), 2.05-2.23 (2H, m), 1.50-1.86 (3H, m). R.T.=1.37; [M+H]+=309.31.

1. stirringthe mixture was stirred at room temperature for 18 hours
2. concentrationThe mixture was concentrated
3. custompurified by silica gel chromatography (5-25% [9:1 methanol:ammonium hydroxide]-ethyl acetate)