Bis-enaminone based parallel solution-phase synthesis of 1,4-dihydropyridine derivatives.
Two variations of a parallel solution-phase synthesis of N-substituted dimethyl 4-oxo-1,4-dihydropyridine-3,5-dicarboxylates 4 and methyl 3-oxo-3,5-dihydro-2H-pyrazolo[4,3-c]pyridine-7-carboxylates 9 from dimethyl acetone-1,3-dicarboxylate (1) were developed. The first synthetic method comprises preparation of the bis-enaminone reagents 2 and 8 and their cyclization with primary amines 3 via double substitution of both dimethylamino groups to give dihydropyridines (DHPs) 4 and 9, respectively. Another variation consists of preparation of the monoenaminone reagents 5 and 10, followed by substitution of the dimethylamino group with primary amines 3, and cyclization of the so formed intermediates 6 with N,N-dimethylformamide dimethylacetal (DMFDMA). In this manner, a library of 46 analytically pure compounds, 24 intermediates 6, 11, and 13, and 22 final dihydropyridines 4 and 9 was obtained employing just a simple filtration workup.
Baskovc
Jernej
J
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia.
Bevk
David
D
Stanovnik
Branko
B
Svete
Jurij
J
D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003500:Cyclization; D003959:Diamines / Q000138:chemical synthesis* / Q000737:chemistry; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000737:chemistry
D000588:Amines; D003959:Diamines; D004095:Dihydropyridines; C038806:1,4-dihydropyridine