Figure 2. Synthesis of WRR-483 (2):

(a) (i) benzyl alcohol (BnOH), 4-dimethylaminopyridine, 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (EDC), N-methylmorpholine, CH₂Cl₂; (ii) piperidine, CH₂Cl₂, 90% (two steps); (b) (i) triphosgene, sodium bicarbonate (NaHCO₃), CH₂Cl₂; (ii) N-methylpiperazine, CH₂Cl₂, 93% (two steps); (c) H₂, 5% palladium on carbon (Pd/C), MeOH, 92% (d) (i) trifluoroacetic acid (TFA), CH₂Cl₂; (ii) 6, N-hydroxybenzotriazole (HOBT), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (EDC), N-methylmorpholine, dimethyl formamide (DMF), CH₂Cl₂, 84%; (g) 3:1 TFA:CH₂Cl₂, 86%.