Development and Scale-Up of an Enabling SyntheticRoute to <b>KTX-005</b>, a Muscarinic Acetylcholine ReceptorAgonist for the Potential Treatment of Schizophrenia

Development and optimization of phase-appropriate synthetic technologies to prepare <b>KTX-005</b>, a potent muscarinic acetylcholine receptor agonist, are described in this article. The modular strategy involves three building blocks: commercially available materials dichlorothiadiazole (<b>21</b>), butanethiol (<b>22</b>), and custom-synthesized azabicyclo derivative (<b>18</b>). The highlight of the enabling synthetic strategy toward <b>KTX-005</b> is a unique thiadiazole ring opening/closing sequence to facilitate both dichlorothiadiazole desymmetrization with butanethiol as well as functionalization of the azabicyclo ring derivative <b>18</b>.