Cesium carbonate → (R)-N-(6-methoxypyrimidin-4-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine

関与物質

反応手順

To (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (from Step B of Example 21) (0.34 g, 1.49 mmol) in N,N-dimethylformamide (15 mL) was added Cs2CO3 (1.22 g, 3.74 mmol) and 4-isothiocyanato-6-methoxypyrimidine (0.25 g, 1.5 mmol). The suspension was stirred at room temperature for 30 minutes. N,N′-diisopropylcarbodiimide (0.7 mL, 4.5 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 (5-15% [9:1 methanol:ammonium hydroxide]/chloroform) to afford (R)—N-(6-methoxypyrimidin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (0.21 g, 0.72 mmol, 48.2% yield) as a white solid. M.P. 186-8° C. 1H NMR (400 MHz, MeOD) δ ppm 8.40 (1H, s), 6.17 (1H, br. s.), 3.92-4.04 (1H, m), 3.89 (3H, s), 3.68 (1H, d, J=10.32 Hz), 3.12-3.23 (1H, m), 2.98-3.12 (1H, m), 2.67-2.97 (4H, m), 2.11 (2H, br. s.), 1.48-1.82 (3H, m). MS (LC/MS) R.T.=0.82; [M+H]+=290.3.

情報源と証拠