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Rapid synthesis of F‐18 and H‐2 dual‐labeled altanserin, a metabolically resistant PET ligand for 5‐HT 2a receptors
Author(s) -
Tan PingZhong,
Baldwin Ronald M.,
Fu Tao,
Charney Dennis S.,
Innis Robert B.
Publication year - 1999
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/(sici)1099-1344(199905)42:5<457::aid-jlcr206>3.0.co;2-0
Subject(s) - chemistry , yield (engineering) , hydrolysis , ligand (biochemistry) , receptor , nitro , specific activity , acetic acid , chloride , medicinal chemistry , nuclear chemistry , stereochemistry , organic chemistry , enzyme , biochemistry , materials science , alkyl , metallurgy
F‐18 and H‐2 dual‐labeled altanserin ( 3 , [ 18 F]d‐ALT), a novel PET tracer for 5‐HT 2A receptors with metabolically resistant properties, was synthesized by [ 18 F]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‐d 2 )carbamate ( 7 ) was obtained by LiA1D 4 reduction of a glycine ester (93%), chlorination and carbamoylation (79%). 4‐(4‐Nitro‐benzoyl)piperidine ( 13 ) was synthesized (60%) by improving the published coupling reaction of p ‐nitrophenyltrimethylstannane ( 10 ), obtained from p ‐iodonitrobenzene and (CH 3 ) 6 Sn 2 (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%). Copyright © 1999 John Wiley & Sons, Ltd.