Syntheses of [4-14C] and [6-14C]nisoldipine

The synthesis of the antihypertensive and antianginal drug [4-14C]nisoldipine started from dimethyl [14C]formamide which was allowed to react with 2-nitrophenyl-lithium yielding 2-nitro[7-14C]benzaldehyde. Knoevenagel condensation with isobutyl acetoacetate yielded isobutyl 2-(2-nitro[7-14C]benzylidene) acetoacetate. The 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-nitro-phenyl)-[4-14C]pyridine-3,5-dicarboxylate (= [4-14C]nisoldipine). (author)