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

To (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.170 g, 0.742 mmol) in N,N-dimethylformamide (20 mL) was added Cs2CO3 (0.604 g, 1.854 mmol) and 4-isothiocyanato-6-phenoxypyrimidine (0.17 g, 0.742 mmol). The suspension was stirred at room temperature for 30 minutes. N,N′-diisopropylcarbodiimide (0.347 mL, 2.225 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% 9:1 methanol:ammonium hydroxide-ethyl acetate) to afford (R)—N-(6-phenoxypyrimidin-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 pale yellow solid. 1H NMR (500 MHz, MeOD) δ ppm 8.43 (1 H, s), 7.47 (2 H, t), 7.30 (1 H, t), 7.16 (2 H, d), 6.21 (1 H, br. s.), 4.03 (1 H, d), 3.72 (1 H, d), 3.22 (1 H, d), 3.11 (1 H, d), 2.73-2.99 (4 H, m), 2.00-2.18 (2 H, m), 1.54-1.88 (3 H, m). LCMS R.T.=1.46; [M+H]+=352.19.

1. stirringto stir 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)

ORD record

ord-f4390104ac6343748b55411ee6a8823e

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07863291B2