Rapid synthesis of F-18 and H-2 dual-labeled altanserin. A metabolically resistant PET ligand for 5-HT(2A) receptors

Article abstract of DOI:10.1002/(SICI)1099-1344(199905)42:5<457::AID-JLCR206>3.0.CO;2-0

F-18 and H-2 dual-labeled altanserin (3, [¹⁸F]d-ALT), a novel PET tracer for 5-HT(2A) receptors with metabolically resistant properties, was synthesized by [¹⁸F]fluoride displacement of the corresponding deuterated nitro precursor in 32% yield (EOB) in 108 min with radiochemical purity 95% and specific activity > 1000 mCi/μmol (EOS). The key intermediate ethyl N-(2-chloroethyl-2,2-d₂)carbamate (7) was obtained by LiAID₄ reduction of a glycine ester (93%), chlorination and carbamoylation (79%). 4-(4-Nitrobenzoyl)piperidine (13) was synthesized (60%) by improving the published coupling reaction of p-nitrophenyltrimethylstannane (10), obtained from p-iodonitrobenzene and (CH₃)₆Sn₂ (94%), with 1-benzoylisonipecotic acid chloride (11) followed by acid hydrolysis. 13 was alkylated with 7 (82%), hydrolyzed and condensed with methyl o-isothiocyanatobenzoyate to provide with the precursor deuteronitroaltanserin (4, 75%).