To a stirred suspension of triphenylphosphine methoxymethane chloride (28.7 mg, 0.084 mmol) in tetahydrofuran (1 ml) was flushed with nitrogen for three times and at 0° C., and was added LiHMDS (0.079 ml, 0.084 mmol). The reddish solution was stirred at 0° C. for 30 minutes, and then at −78° C., a solution of 1-(4-(5-((5-cyclobutyl-1,3,4-oxadiazol-2-yl)amino)pyridin-2-yl)phenyl)-2-oxabicyclo[2.2.2]octane-4-carbaldehyde (30 mg, 0.070 mmol) in tetrahydrofuran (0.7 ml) was added dropwise. The mixture was allowed to warm to 0° C. for 30 minutes. The reaction was quenched with water (2 ml), and the mixture was partitioned between brine (15 ml) and ethyl acetate (50 ml), aquous layer was extracted with ethyl acetate (2×50 ml). The combined organic extracts were washed with brine and dried over Na2SO4, and concentrated. The residue was purified by flash chromatography (heptanes/acetone 1/1) to afford 5-cyclobutyl-N-(6-(4-(4-(2-methoxyvinyl)-2-oxabicyclo[2.2.2]octan-1-yl)phenyl)pyridin-3-yl)-1,3,4-oxadiazol-2-amine (10 mg, 31%) as yellow solid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.83-2.51 (m, 14H) 3.56 (s, 3H) 3.63-3.76 (m, 1H) 4.00 (d, J=6.80 Hz, 1H) 4.06 (s, 2H) 5.87 (d, J=6.80 Hz, 1H) 7.49 (d, J=8.72 Hz, 2H) 7.78-7.93 (m, 3H) 8.17 (dd, J=24.00, 8.80 Hz, 1H) 8.71 (d, J=16.80 Hz, 1H). LC/MS, [MS+1] 459.1, RT: 1.44, 1.48; (Condition E).
