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

To (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.363 g, 1.583 mmol) in N,N-dimethylformamide (20 mL) was added Cs2CO3 (1.289 g, 3.96 mmol) and 4-isothiocyanato-6-(3-methoxyphenyl)pyrimidine. The suspension was stirred at room temperature for 30 minutes. N,N′-diisopropylcarbodiimide (0.740 mL, 4.75 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-methoxypyrimidin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (0.294 g, 0.788 mmol, 50% yield) as a a pale yellow solid. M.P 80-5° C. 1H NMR (400 MHz, MeOD) δ ppm 8.77 (1H, s), 7.47-7.58 (2H, m), 7.39 (1H, t), 7.20 (1H, br. s.), 7.04 (1H, dd), 4.05 (1H, d), 3.85 (3H, s), 3.74 (1H, d), 3.23 (1H, d), 3.10 (1H, d), 2.71-3.00 (4H, m), 2.03-2.22 (2H, m), 1.53-1.85 (3H, m). MS (LC/MS) R.T.=1.58; [M+H]+=366.15.

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-Eintrag

ord-bf1a60071d19495781da599be6bb943c

Quelldatensatz

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08309577B2