For the synthesis of umespirone the following synthesis pathway was chosen: Acetone is condensed with ethyl cyanoethanoate (I) to yield ethylisopropylidenecyanoacetate (II). This product is reacted with N-butylcyanoacetamide (III) in sodium methoxide solution to give N-butyl-2,4-dicyano-3,3-dimethylglutarimide (IV). The glutarimide (IV) is cyclized with phosphoric acid to yield 3-butyl-9,9-dimethyl-3,7-diazabicyclo[3.3.1]nonane-2,4,6,8-tetraone (V). The quaternary salt (VIII) (R = CH3), prepared from 1-(2-methoxyphenyl)piperazine (VI) and 1,4-dibromobutane (VII), undergoes reaction with (V) in the presence of potassium carbonate to afford the free base KC-9172 (IX) (R = CH3).

For the synthesis of umespirone the following synthesis pathway was chosen: Acetone is condensed with ethyl cyanoethanoate (I) to yield ethylisopropylidenecyanoacetate (II). This product is reacted with N-butylcyanoacetamide (III) in sodium methoxide solution to give N-butyl-2,4-dicyano-3,3-dimethylglutarimide (IV). The glutarimide (IV) is cyclized with phosphoric acid to yield 3-butyl-9,9-dimethyl-3,7-diazabicyclo[3.3.1]nonane-2,4,6,8-tetraone (V). The quaternary salt (VIII) (R = CH3), prepared from 1-(2-methoxyphenyl)piperazine (VI) and 1,4-dibromobutane (VII), undergoes reaction with (V) in the presence of potassium carbonate to afford the free base KC-9172 (IX) (R = CH3).