Reaction Steps
To 2-isothiocyanato-6-methoxy-[1,2,4]triazolo[1,5-a]pyridine (160 mg, 0.78 mmol) in N,N-dimethylformamide (5 ml) was added (S)-3-(aminomethyl)quinuclidin-3-ol, 2HCl (178 mg, 0.78 mmol) and triethylamine (0.32 ml, 2.33 mmol). The reaction was stirred at 70° C. for 1 hour. N,N′-Diisopropylcarbodiimide (0.36 ml, 2.33 mmol) was then added to the reaction mixture. The mixture was heated at 70° C. for 4 hours, then cooled and poured into aqueous sodium bicarbonate/chloroform. The product was extracted (3×) with chloroform. The combined organics were washed with water (3×), dried over sodium sulfate, filtered, and concentrated in vacuo, then purified via flash chromatography (2-20% [10% ammonium hydroxide:methanol]/chloroform) to yield (R)—N-(6-methoxy-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-4H-1′-azaspiro-[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (114.5 mg, 0.33 mmol, 42% yield) as a white powder. 1H NMR (500 MHz, CDCl3) δ ppm 8.51 (1H, br. s.), 8.08 (1H, d, J=2.44 Hz), 7.35 (1H, d, J=9.77 Hz), 7.18 (1H, dd, J=9.46, 2.44 Hz), 3.92 (1H, d, J=8.85 Hz), 3.84 (3H, s), 3.58 (1H, d, J=8.85 Hz), 3.36-3.41 (1H, m), 2.72-3.05 (4H, m), 2.18-2.26 (1H, m, J=13.26, 9.98, 3.66, 3.49, 3.49 Hz), 2.13 (1H, br. s.), 1.79 (1H, br. s.), 1.67-1.76 (1H, m, J=13.96, 9.84, 4.27, 4.27 Hz), 1.45-1.63 (2H, m). MS (LC/MS) R.T.=0.86; [M+H]+=329.2.
