Cesium carbonate → HCID 59286606, compound

Participants

Reaction Steps

To a stirring suspension of (S)-3-(ammoniomethyl)-3-hydroxy-1-azoniabicyclo[2.2.2]octane chloride (73 mg, 0.319 mmol) and cesium carbonate (221 mg, 0.678 mmol) in DMF (5 mL) was added a solution of 3-isothiocyanato-6,7-dimethoxyisoquinoline (69 mg, 0.280 mmol) in DMF (1.5 mL) and the reaction mixture was allowed to stir at room temperature for 3 days. To the solution was then added a solution of N,N′-methanediylidenedipropan-2-amine (69 mg, 0.547 mmol) in DMF (0.4 mL) and the reaction was allowed to stand at room temperature for 14 days. Another 69 mg di-isopropylcarbodiimide was added in −0.4 mL acetonitrile and the reaction was allowed to stand for 1 more day, then it was evaporated in vacuo and the residue subjected to preparative HPLC to yield (R)—N-(6,7-dimethoxyisoquinolin-3-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine 20.9 mg. (8%) LCMS RT 0.98 min, MH+=403.2 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.73 (1H, s), 7.28 (1H, s), 7.09 (1H, s), 6.96 (1H, s), 4.01 (3H, s), 4.00 (3H, s), 3.96 (1H, d, J=8.5 Hz), 3.63 (1H, d, J=9.2 Hz), 3.39 (1H, d, J=15.0 Hz), 2.79-3.10 (5H, m), 2.24 (1H, br. s.), 2.15 (1H, br. s.), 1.75 (1H, dddd, J=13.9, 9.3, 4.7, 4.4 Hz), 1.59-1.68 (1H, m), 1.48-1.59 (1H, m)

Provenance & Evidence