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

Participants

Reaction Steps

To (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.111 g, 0.484 mmol) in N,N-dimethylformamide (15 mL) was added Cs2CO3 (0.395 g, 1.211 mmol) and 4-(3-chlorophenyl)-6-isothiocyanatopyrimidine (0.12 g, 0.484 mmol). The suspension was stirred at room temperature for 30 minutes. N,N′-diisopropylcarbodiimide (0.226 mL, 1.453 mmol) was then added and the mixture was continued to stir at room temperature for 18 hours. The mixture was concentrated and purified by silica gel chromatography (5-25%, then, 2-10% 9:1 methanol:ammonium hydroxide-ethyl acetate) to afford (R)—N-(6-(3-chlorophenyl)pyrimidin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (0.086 g, 0.221 mmol, 46% yield) as a yellow solid. 1H NMR (400 MHz, MeOD) δ ppm 8.82 (1 H, d), 8.05 (1 H, d), 7.93 (1 H, ddd), 7.43-7.52 (2 H, m), 7.35 (1 H, br. s.), 4.13 (1 H, d), 3.93 (1 H, d), 3.63-3.81 (2 H, m), 3.42-3.53 (1 H, m), 3.30-3.40 (3 H, m), 2.46 (1 H, d), 2.26-2.40 (1 H, m), 1.88-2.16 (3 H, m). LCMS R.T.=1.90; [M]+=370.28.

Provenance & Evidence