Pyrimidine-4-carboxylic ester, 1,6-dihydro

Hydrazinolysis of the imidate and carboxylic ester functions of 1-aryl-oxycarbonyl-l,6-dihydro-2-methoxypyrimidines (61) with 1 molar equivalent of hydrazine hydrate culminated in the formation of the 1,2,4-tria-zolo[4,3-a]pyrimidine-3-ones 63 [89GEP(0)3839711] (Scheme 25). 

K.S. Atwal, G.C. Rovnyak, S.D. Kimball, D.M. Floyd, S. Moreland, B.N. Swanson, J.Z. Gougoutas, J. Schwartz, K.M. SmiUie, M.F. Malley, Dihydropyrimidine calcium channel blockers. 11. 3-Substituted-4-aryl-l,4-dihydro-6-methyl-5-pyrimidine carboxylic acid esters as potent mimics of dihydropyridines, J. Med. Chem. 33 (1990) 2629-2635. 

Bahrami K, Khodaei MM, Farrokhi A (2009) Highly efficient solvent-free synthesis of dihydropyrimidinones catalyzed by zinc oxide. Synth Commun 39 1801-1808 74. Gross GA, Wurziger H, Schober A (2006) Solid-phase synthesis of 4,6-diaryl-3,4-dihydro-pyrimidine-2(lH)-one-5-carboxylic acid amide derivatives a Biginelli three-component-condensation protocol based on immobilized beta-ketoamides. J Comb Chem 8 153-155 Desai B, Dallinger D, Kappe CO (2006) Microwave-assisted solution phase synthesis of dihydropyrimidine C5 amides and esters. Tetrahedron 62 4651 664 Kumar A, Maurya RA (2007) An efficient bakers yeast catalyzed synthesis of 3,4-dihydro-pyrimidin-2-(lH)-ones. Tetrahedron Lett 48 4569-4571 77. Zalavadiya P, Tala S, Akbari J, Joshi H (2009) Multi-component synthesis of dihydropyrimidines by iodine catalyst at ambient temperature and in-vitro anti mycobacterial activity. Arch Pharm 342 469-475... 

A derivative of a hitherto unknown nucleus was produced when 4-amino-5-aminomethyl-3-methyltriazole was refluxed with carbon disulfide and triethylamine in pyridine, which yielded 3-methyl-3,7-dihydro-l,2,3-triazolo-[4,5-d][l,3]thiazine-5-thione (98) (3 hr, 53%) the 3-benzyl analog was made similarly (63%) [80JCS(P1)2009]. Cyclization of 4-anilino-5-ethoxycarbonyltriazole with polyphosphoric acid produced 1 f/-triazolo-[4,5-h]quinol-4-one (99) [80EUP(A)2562]. Similarly, ring closure of 4-(2-pyridylamino)triazole-5-carboxylic acid (or its esters) gave l//-pyrido-[l,2-a]-l,2,3-triazolo[4,5-d]pyrimidin-4-one (100) (77GEP2757929). 4-Amino-5-formyl-3-methyltriazole and pentane-2,4-dione, set aside in 20% sulfuric acid, yielded 3,5-dimethyl-3//-l,2,3-triazolo [4,5-6] pyridin-6-yl... 

Many ring-fused imidazole derivatives have been synthesized by various methods. Domino Michael addition retro-ene reaction of 2-alkoxyiminoimidazolidines and acetylene carboxylates provided a synthesis of 2,3-dihydroimidazo[l,2-a]pyrimidin-5-(l//)-ones <05T5303>. A single step synthesis of 3,5-dialkyl-9-nitroimidazo[l,2-c]quinazolin-2(3//)-ones from simple carbonyl compounds, primary amines or amino acid methyl esters and 2-azido-5-nitrobenzonitrile has been published <05TL5778>. Diels-Alder reaction of azadienes and benzimidazole-4,7-diones afforded imidazo[4,5-g ]quinoline-4,9-dione derivatives <05EJ01903>. Reaction between isocyanides and dialkyl acetylenedicarboxylates in the presence of 4,5-diphenyl-l,3-dihydro-2//-imidazol-2-one provided a one-pot synthesis of 5//-imidazo[2,l-ft][l,3]oxazine derivatives <05T2645>. Microwave irradiation was employed in the synthesis of 1-ary 1-3-acetyl-1,4,5,6-... 

Enzymological and pharmacological properties of 2-(2-methylpyridin-4-yl)methyl-4-(3,4,5-trimethoxyphenyl-8-(pyrimidin-2-yl)methoxy-l,2-dihydro-l-oxo-2,7-naphthyridine-3-carboxylic add methyl ester hydrochloride, a new phosphodiesterase type 5 inhibitor, were studied in vitro and in vivo (2002MI6). 

The increased potency of the pyrido 2,3-d]pyrimidine ester (111) and the achievement of oral activity with the benzo[ quinazoline ester (V) suggested the preparation of 3,4-dihydro-4-oxopyrimido[4,5-b]quinoline-2-carboxylic acid (VI) and its corresponding ethyl ester (VII) which combine the features of III and V. This new acid and ethyl ester exhibit PCA activity 4 to 8 times that of DSCC and thus are about 50 to 100 times... 

Fused pyrimidine-2 carboxylic acids Thienopyrimidines (22,74) and pyrimidoquinoxalines (75). both of which are related to our pyrimido-[4,5-b]quinoline-2-carboxylic acid esters (XXXV and XLIII), were recently reported in the patent literature by Mead Johnson and Mitsubishi, respectively. The most potent compound in the thienopyrimidine series is XCVIII which has an oral ED50 of 3.1 mg/kg (Z3), while ethyl 7,8-di-methoxy-3,4-dihydro-4-oxopyrimido[5,6-b]quinoxaline-2-carboxylate (XCIX) appears to be about equipotent (25) with our compound XXXV. 

Two examples of monocyclic 1,3,4-oxadiazepines have been reported. The fully unsaturated compounds have, however, not been isolated, although the photolysis of pyrimidine. iV-oxides is known to involve such oxadiazepines as unisolable intermediates <69TL4899>. 2-Benzoylpropene or 2-benzoylpropanol condensed with hydrazine hydrate and an appropriate carboxylic acid to form the hydrazone esters (133), which were converted into the 6,7-dihydro-l,3,4-oxadiazepines (134) (30 72% yields) by intramolecular attack of the amino group to the ester carbonyl, followed by acid-catalyzed loss of water (Scheme 23) <84S342>. 

R = H, D) were obtained from the 6-methyl-3-ester derivative and its 6,7,8-deuterio derivative 291 (R = Me, R = COOEt, R -R" = H, D). These derivatives were transformed into 293 (R = H, D) by heating in POCI3. Optically active 291 (R = Me, R = COOEt, R -R = H) afforded optically active 6,7-dihydro-477 294 (R = H), but optically inactive AH-pyrido[l, 2-a]pyrimidine 293 (R = Me, R = COOEt, R = H). Similarly ethyl 9-(A -phenyl-iV-methylamino)-6-methyl-4-oxo-6,7-dihydro-4/7-pyrido[l,2-a] pyrimidine-3-carboxylate gave 9-[iV-(4-formylphenyl)-A -methylamino]-7-dimethylaminomethylene-6-methyl-6,7-dihydro-4-oxo-4/f-pyrido[l,2-u]pyr-imidine-3-carboxylates in a mixture of POCI3 and DMF at lower (20-25 °C) and higher (95 100°C) temperatures, respectively. 9-(Ethoxycarbonyl-methyl)-4-oxo-6,7-dihydro-47/-pyrido[l,2-a]pyrimidine-3-carboxylate 158 (but not 9-ethoxycarbonylmethylene-6,7,8,9-tetrahydro derivative 157) was also transformed into ethyl 9-(ethoxycarbonylmethyl)-7-(l-chloroethyl)-4-oxo-477-pyrido[l, 2-a]pyrimidine-3-carboxylate (99T10221). 

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