Umespirone (KC-9172) is a drug of the azapirone class which possesses anxiolytic and antipsychotic properties. It behaves as a 5-HT<sub>1A</sub> receptor partial agonist (K<sub>i</sub> = 15 nM), D<sub>2</sub> receptor partial agonist (K<sub>i</sub> = 23 nM), and ñ<sub>1</sub>-adrenoceptor receptor antagonist (K<sub>i</sub> = 14 nM), and also has weak affinity for the sigma receptor (K<sub>i</sub> = 558 nM). Unlike many other anxiolytics and antipsychotics, umespirone produces minimal sedation, cognitive/memory impairment, catalepsy, and extrapyramidal symptoms.
The condensation between ethyl cyanoacetate (1) and acetone gives ethylisopropylidenecyanoacetate [759-58-0] (2). This product is reacted with N-butylcyanoacetamide [39581-21-0] (3) in sodium methoxide solution to give N-butyl-2,4-dicyano-3,3-dimethylglutarimide, CID:10681941 (4). The glutarimide is cyclized with phosphoric acid to yield 3-butyl-9,9-dimethyl-3,7-diazabicyclo[3.3.1]nonane-2,4,6,8-tetraone, https://pubchem.ncbi.nlm.nih.gov/compound/10825633 CID:10825633 (5).
The reaction between 1-(o-anisyl)piperazine [35386-24-4] (6) and 1,4-dibromobutane [110-52-1] (7) gives the Quat salt CID:15895413(8).
Convergent synthesis (in the presence of potassium carbonate) affords ' (KC-9172) (9).