合成路线1

The synthesis of [3H]-labeled robalzotan has been described: The bromination of 3(R)-(dicyclobutylamino)-8-fluoro-5-methoxy-3,4-dihydro-2H-benzopyran (I), a previously described intermediate in the synthesis of robalzotan, with Br2 in ethanol affords the 6-bromo-8-fluorobenzopyran derivative (II), which is first demethylated with refluxing conc. HBr yielding the 5-hydroxy compound (III) and then treated with Tf2O in dichloromethane providing triflate (IV). The carbonylation of (IV) with CO and Pd(OAc)2 in DMF/methanol gives the methyl ester (V), which is hydrolyzed with refluxing HCl to yield the carboxylic acid (VI). The reaction of (VI) with SOCl2 affords the corresponding acyl chloride (VII), which is treated with ammonia to provide the carboxamide (VIII). Finally, this compound is hydrogenated with 3H2 catalyzed by PdO in DMF.