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Isosteres Oxygenes d'Hydroxy‐di‐n‐Propylaminotetralines Syntheses de Monomethoxy et Monohydroxy‐ (DI‐N‐Propylamino)‐3 Chromannes [n‐Propyl‐ 3 H] Racemiques: Nouveaux Radioligands des Sites de Liaison Serotoninergiques 5‐HT 1a et Dopaminergiques D 2
Author(s) -
Cossery J. M.,
Perdicakis C.,
Coudert G.,
Guillaumet G.,
Pichat L.
Publication year - 1988
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/jlcr.2580250805
Subject(s) - chemistry , hydrogenolysis , stereochemistry , iodide , acetonitrile , methanol , high performance liquid chromatography , catalysis , medicinal chemistry , organic chemistry
Abstract Oxygen Isosteres of hydroxy‐di‐n‐propylaminotetralines. Syntheses of racemic monomethoxy and monohydroxy‐3‐(di‐n‐[ 3 H‐propyl] amino) chromanes: new Radioligands for 5–HT 1A and D 2 receptors sites labelling. Condensation of monomethoxy salicylaldehydes: 4a – d with nitroethanol gave methoxy‐3‐nitro‐2H chromenes 5a – d which were reduced with LAH into methoxy‐3‐amino chromans 6a – d . Two syntheses of 2‐hydroxy‐6‐methoxy‐benzal‐dehyde: 4a were described. N‐alkylations of 6a – d were carried out a/ by Borch procedure b/ by n‐propylation with propyl iodide in presence of bases c/ by allylation in presence of bases. Methoxy‐3‐(diallyl‐amino) chromans: 13a – d were catalytically reduced with hydrogen (Pd/C in methanol) into mixtures of methoxy‐3 (di‐n‐propylamino) chromans 2a – d and methoxy‐3‐ (n‐propylamino) chromans resulting from the hydrogenolysis of one allyl group. Methoxy‐3‐dialkylamino chromans 2a – d and 13a were O‐demethylated either by boiling 48% HBr or by BBr 3 in CH 2 Cl 2 . Catalytic hydrogenation with tritium of precursors 13a – d and 15a in methanol in presence of 10% Pd/C gave [ 3 H] – 5. OH‐DPLC: 3a ; [ 3 H] 5. OMe‐DPAC: 2a and the isomers: 2b ‐ 2d which were purified by HPLC, analyzed by reversed HPLC, 3 H‐NMR, M.S. (spec. radioactivity: 37.2‐80 Ci/μMole. Radiochemical purity: 98.3–99.6%).