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

Beteiligte Stoffe

Reaktionsschritte

To (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.39 g, 1.71 mmol) in dimethylformamide was added cesium carbonate (1.39 g, 4.28 mmol) and 4-isothiocyanato-6-(methoxymethyl)pyrimidine (0.31 g, 1.71 mmol). The suspension was stirred at ambient temperature for 15 min. To the reaction mixture was added N,N′-diisopropylcarbodiimide (0.80 mL, 5.13 mmol) and the mixture was stirred overnight then concentrated. The residue was purified by column chromatography (5-25% 9:1 methanol/ammonium hydroxide in ethyl acetate) to afford (R)—N-(6-(methoxymethyl)pyrimidin-4-yl)-4 H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (0.18 g, 0.58 mmol, 34% yield) as a yellow solid. 1H NMR (400 MHz, MeOD-d4) δ ppm 8.65 (1 H, d, J=1.01 Hz), 6.92 (1 H, br. s.), 4.40 (3 H, s), 4.03 (1 H, d, J=10.32 Hz), 3.72 (1 H, d, J=10.32 Hz), 3.44 (2 H, s), 3.18-3.26 (1 H, m), 3.06-3.13 (1 H, m), 2.69-2.96 (4 H, m), 1.94-2.19 (2 H, m), 1.45-1.86 (3 H, m). MS (LC/MS) R.T.=0.76; [M+H]+=304.30.

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