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

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Reaction Steps

To (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.13 g, 0.560 mmol) in N,N-dimethylformamide (20 mL) was added Cs2CO3 (0.46 g, 1.4 mmol) and 4-isothiocyanato-6-(pyridin-3-yl)pyrimidine (0.12 g, 0.56 mmol). The suspension was stirred at room temperature for 30 minutes. N,N′-Diisopropylcarbodiimide (0.26 mL, 1.7 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 (0-10% [9:1 methanol:ammonium hydroxide]-ethyl acetate) to afford (S)—N-(5-chloropyrazin-2-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (0.182 g, 0.613 mmol, 35% yield) as an off-white solid. 1H NMR (400 MHz, MeOD) δ ppm 9.13-9.21 (1H, m), 8.82 (1H, d), 8.63 (1H, dd), 8.44 (1H, dt), 7.56 (1H, dd), 7.31 (1H, s), 4.06 (1H, d), 3.76 (1H, d), 3.20-3.28 (1H, m), 3.08-3.16 (1H, m), 2.72-3.01 (4H, m), 2.00-2.24 (2H, m), 1.52-1.83 (3H, m). LCMS R.T.=0.72; [M+H]+=337.2.

Provenance & Evidence