Development of a two-step route to 3-PBC and ßCCt, two agents active against alcohol self-administration in rodent and primate models.

To gain access to 3-propoxy-ß-carboline hydrochloride (3-PBC·HCl) (1·HCl) and ß-carboline-3-carboxylate-tert-butyl ester (ßCCt) (2), potential clinical agents active against alcohol self-administration, a two-step route was developed. This process involves a palladium-catalyzed Buchwald-Hartwig coupling and an intramolecular Heck reaction. This two-step route provides rapid access to multigram quantities of 3-PBC (1) and ßCCt (2), as well as analogues for studies of alcohol self-administration. The overall yield of 3-PBC (1) was improved from 8% to 50% by this route.