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Syntheses of [4‐ 14 c] and [6‐ 14 c]nisoldipine
Author(s) -
Scherling D.,
Pleiß U.
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.2580251213
Subject(s) - chemistry , nisoldipine , meldrum's acid , medicinal chemistry , mesityl oxide , dimethyl carbonate , ethyl acetoacetate , toluene , pyridine , methanol , organic chemistry , nuclear chemistry , catalysis , nifedipine , calcium
The synthesis of [4‐ 14 C]nisoldipine started from dimethyl [ 14 C]formamide which was allowed to react with 2‐nitrophenyllithium yielding 2‐nitro[7‐ 14 C]benzaldehyde. Knövenagel condensation with isobutyl acetoacetate yielded isobutyl 2‐(2‐nitro[7‐ 14 C]benzylidene) acetoacetate. Key reaction step was the cyclizing Michael addition with methyl 3‐aminocrotonate to obtain 3‐isobutyl 5‐methyl 1, 4‐dihydro‐2, 6‐dimethyl‐4‐(2‐nitrophenyl)‐[4‐ 14 C]pyridine‐3,5‐dicarboxylate (= [4‐ 14 C]nisoldipine). Starting material of the synthesis of [6‐ 14 C]nisoldipine was barium[ 14 C]carbonate which was converted to [1‐ 14 C]acetyl chloride. The acid chloride was condensed with Meldrum's acid (2,2‐dimethyl‐1, 3‐dioxane‐4,6‐dione). The resulting intermediate was treated with boiling methanol to give methyl [3‐ 14 C]acetoacetate. Reaction of the ß‐ketoester with gaseous ammonia in toluene afforded the corresponding aminocrotonate, which was condensed with isobutyl 2‐(2‐nitrobenzylidene)‐acetoacetate to yield [6‐ 14 C]nisoldipine.