We prepared photocaged WAY161563 by synthesizing the drug and then conjugating it to the photocage. The synthesis of WAY161563 followed the general procedure of Welmaker et al. with modifications (Scheme 1). Accordingly, a nucleophilic aromatic substitution reaction with 1,2-dichloro-4-fluoro-5-nitrobenzene 1 and commercially available 4-benzyloxycarbonylpiperazine-2-carboxylic acid 2 formed 3 in a 60% yield. Tandem Bechamp reduction-cyclization of 3 formed 4 in 50% yield. The Cbz-amine of 4 was reduced with palladium on carbon under hydrogen atmosphere to yield 5 (WAY-161503) in 66% yield of the racemate. As 5HT2C receptors have been shown not to discriminate between the two enantiomers, they are typically not separated when preparing this drug. To install the cage, WAY161503 was condensed with commercially available WinterGreen photocage carbonyldiimidazole adduct 6 following the method of Peterson et al. to provide the caged compound 7 in 58% yield. Caged antagonist N-desmethylclozapine was synthesized by first demethylating clozapine following the method of McRobb et al. Briefly, 1-chloroethyl chloroformate added to a solution of clozapine 8 heated to reflux for 24 hr. The crude reside was dissolved in methanol and heated at 50 °C for 2 h to yield N-desmethylclozapine 9 in a 53% yield. Commercially available WinterRed photocage 12 was condensed with carbonyldiimidazole to form the carbamoyl imidazole adduct. The adduct is then incubated with desmethylclozapine 9 to provide WinterRed photocaged desmethylclozapine 14 in 52% yield (Scheme 2).