3-Nitrobenzaldehyde → 3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-, 3-(2-cyanoethyl) 5-methyl ester

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Reaction Steps

Compounds of formula 1 may also be prepared via Scheme IV. A dihydropyridine of formula 12 is prepared as in Scheme I, and the compound condensed with an intermediate of formula 9 to form a compound of formula 1. For example, methyl 3-aminocrotonate, 3-nitrobenzaldehyde, and 2-cyanoethyl 3-oxobutanoate are heated together to form 2,6-dimethyl-3-carbomethoxy-4-(3-nitrophenyl)-5-(2-cyano)ethoxycarbonyl-1,4-dihydropyridine. The cyanoethyl ester is hydrolyzed using NaOH followed by HCl, converted to an acid halide (e.g., using thionyl chloride), and condensed with a compound of the formula HO--A--X, for example, 3-bromopropanol, to form a compound of formula 12. For example, 2,6-dimethyl-3-carbomethoxy-4-(3-nitrophenyl)-5-(2-cyano)ethoxycarbonyl-1,4-dihydropyridine is treated sequentially with NaOH, HCl, and thionyl chloride, then condensed with 3-bromopropanol to form 2,6-dimethyl-3-carbomethoxy-4-(3-nitrophenyl)-5-(3-bromopropoxycarbonyl)-1,4-dihydropyridine (12). The resulting bromo derivative is then condensed with 4-(2-tetrahydropyran-2-yloxyethyl)phenol to form 2,6 -dimethyl-3-carbomethoxy-4-(3-nitrophenyl)-5-(3-[4-(2-tetrahydropyran-2-yloxyethyl)phenyl]propoxycarbonyl)-1,4-dihydropyridine (1).

Provenance & Evidence