1,1'-Carbonyldiimidazole → 5-Chloro-2-methoxy-4-(methylamino)-N-[2-(1-pyrrolidinyl-methyl)-1-azabicyclo[2.2.2]oct-3-yl]benzamide

Participants

Reaction Conditions

Reaction Steps

a suspension of 5-chloro-2-methoxy-4-(methylamino)benzoic acid (3.13 g, 14.5 mmoles) in anhydrous tetrahydrofuran (20 ml) under nitrogen was treated with 1,1'-carbonyldiimidazole (2.44 g, 15 mmoles), stirred for 90 minutes, cooled (0° C.), and treated with 2-(1-pyrrolidinylmethyl)-1-azabicyclo[2.2.2]octane-3-amine (3.14 g, 15.0 mmoles) in anhydrous tetrahydrofuran (10 ml). After 24 hours at room temperature and one hour at 60° C., the solution was concentrated in vacuo and partitioned between methylene chloride (100 ml) and 1.0N aqueous sodium carbonate (50 ml). The organic layer was separated and the aqueous solution was extracted with methylene chloride (40 ml). The combined organic solution was washed with brine (50 ml), dried (Na2SO4), concentrated in vacuo, dissolved in tetrahydrofuran, and filtered. The filtrate was passed through alumina (eluted with 15% methanol/ethyl acetate), and concentrated in vacuo to provide 3.71 g (63%) of a colorless foam.

Provenance & Evidence