Avatrombopag

It acts as a thrombopoietin receptor agonist.

Synthesis

The chemical synthesis of avatrombopag was recently reported:

The halogenation of 2-acetyl-4-chlorothiophene [34730-20-6] (1) gave 2-bromo-1-(4-chloro-2-thienyl)ethanone [677007-73-7] (2). Condensation with thiourea produced 4-(4-chlorothiophen-2-yl)-1,3-thiazol-2-amine [570407-10-2] (3). Halogenation with N-bromosuccinimide (NBS) in DMF have an intermediate which was used for nucleophilic aromatic substitution with 1-cyclohexylpiperazine [17766-28-8] (4) to provide [570407-42-0] (5). Schotten-Baumann reaction with 5,6-dichloronicotinic acid [41667-95-2] (6) gave the corresponding nicotinamide [570403-04-2] (7). A second nucleophilic aromatic substitution ethyl isonipecotate [1126-09-6] (8) gave [570403-14-4] (9). Subsequent saponification completed the synthesis of avatrombopag (10).