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Two variations of a parallel solution-phase synthesis of N-substituted dimethyl 4-oxo-1,4-dihydropyridine-3,5-dicarboxylates 4and methyl 3-oxo-3,5-dihydro-2H-pyrazolo[4,3-c]pyridine-7-carboxylates 9from dimethyl acetone-1,3-dicarboxylate (1) were developed. The first synthetic method comprises preparation of the bis-enaminone reagents 2and 8and their cyclization with primary amines 3via double substitution of both dimethylamino groups to give dihydropyridines (DHPs) 4and 9, respectively. Another variation consists of preparation of the monoenaminone reagents 5and 10, followed by substitution of the dimethylamino group with primary amines 3, and cyclization of the so formed intermediates 6with 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 4and 9was obtained employing just a simple filtration workup. [ABSTRACT FROM AUTHOR]

A simple and efficient synthesis of four new substituted pyrimidines, compounds 9a–d, from the title compound 3 is described. Conversion of 3 to methyl (E)-3-(dimethylamino)-2-(6-methoxy-2-phenylpyrimidin-4-yl)prop-2-enoate (4), followed by condensation with various dinucleophiles according to the ‘enaminone methodology’, afforded the target compounds 9 in medium-to-good yields. [ABSTRACT FROM AUTHOR]

Combinatorial solution-phase cycloadditions of (1Z,4R,5R)-4-benzoylamino-5-phenylpyrazolidin-3-on-1-azomethine imines 3to -keto esters 4afforded a library of 26 bicyclic pyrazolidinones 5in 6−89% yields and in 14−100% de. All products were isolated in >90% purity according to 1H NMR, and 25 of them were analytically pure. The structures of cycloadducts were confirmed by NMR and X-ray diffraction. Most of the products were isolated as mixtures of the major (1S,2S,3R,5R,6R)-epimers 5and the minor (1R,2S,3R,5R,6R)-epimers 6. Epimerization of cycloadducts 5/6at the anomeric position 1 in solution was confirmed by 1H NMR. [ABSTRACT FROM AUTHOR]

Solution-phase combinatorial synthesis of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides was studied. First, di-tert-butyl (2S,4S)-4-amino-5-oxopyrrolidine-1,2-dicarboxylate hydrochloride was prepared as the key intermediate in five steps from (S)-pyroglutamic acid. Acylation of the amino group followed by acidolytic deprotection gave (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxylic acids, which were then coupled with amines to furnish a library of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides. Four coupling reagents, BPC, EEDQ, TBTU, and PFTU, were tested for the amidation reactions in the final step. Amidations with EEDQ and TBTU led to the desired carboxamides. On the other hand, BPC and PFTU were not suited, since diketopiperazines were sometimes obtained instead of the desired carboxamides. [ABSTRACT FROM AUTHOR]