5 pyri midine

Azido-l,3-dimethyluracil is converted into l,2,3-triazolo[4,5-reaction with potassium carbonate in DMF, and the presence of alkyl halides affords 1-alkylated products [77H(6) 1915]. Another study reports that the reaction with methyl iodide gives two... 

This approach has been extended by Tieckelmann, Mulvey, and Gottis to 2-amino-5-cyanonicotinamides (16 and 18), whiob were prepared directly by partial hydrolysis of the corresponding dir itriles. Diethyl carbonate, ethyl orthoacetate, and ethyl orthoformate all underwent reaction to yield the corresponding pyrido[2,3-( ]pyri-midines (17 and 19). 

An interesting variation of this procedure relies upon the formation of malondialdehyde precursors in situ. Vinylogs of Vilsmeier-Haack intermediates (60), formed from dimethylaminoacroleins (59) and phosgene, undergo reaction with 2,4,6-triaminopyrimidine to yield 6-alkyl- and 6-aryl-substitutcd 2,4-diaminopyrido[2,3-d]-pyri-midines (61). Dimethylaminoacroleins were found to be unsatisfactory. ... 

Oxidations of pyridopyrimidines are rare, but the covalent hydrates of the parent compounds undergo oxidation with hydrogen peroxide to yield the corresponding pyridopyrimidin-4(3 T)-ones. Dehydrogenation of dihydropyrido[2,3-(i]pyrimidines by means of palladized charcoal, rhodium on alumina, or 2,3-diehloro-5,6-dicyano-p-benzo-quinone (DDQ) to yield the aromatic derivatives have been reported. Thus, 7-amino-5,6-dihydro-1,3-diethylpyrido[2,3-d]-pyri-midine-2,4(lif,3f/)-dione (177) is aromatized (178) when treated with palladized charcoal in refluxing toluene for 24 hours. 

The relative stereostructure of 9-acetyl-7-hydroxy-l,2-dimethyl-7-meth-oxycarbonyl-4-phenyl-6-oxo-l, 4,7,8-tetrahydro-6/7-pyrido[l, 2-u]pyri-midine-3-carboxylate 122 was justified by an X-ray diffraction analysis (97JOC3109). The stereochemistry and solid state structure of racemic trans-6,9-//-l, 6-dimethyl-9 z-ethoxy-9-hydroxy-4-oxo-l,6,7,8,9,9 z-hexahydro-4//-pyrido[l,2- z]pyrimidine-3-carboxylate (123), adopting a cw-fused conformation, were determined by X-ray investigations (97H(45)2175). 

Vilsmeier-Haack formylation of 2-(4-methyl-l-piperazinyl)-4//-pyrido-[l,2-n]pyrimidin-4-one with a mixture of POCI3 and DMF at 95°C gave a 3-formyl derivative (93FES1225) while ethyl 4-oxo-6,7,8, 9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-2-acetate at 50 °C yielded a 9-dimethylaminomethylene-3-formyl derivative (01MI4). 3-Formyl-2-hydroxy-8-[2-(4-isopropyl-l,3-thiazol-2-yl)-l-ethenyl]-4//-pyrido[l,2-n]pyri-midin-4-one was obtained from the 3-unsubstituted derivative with oxalyl chloride-DMF reagent in CH2CI2 at room temperature for 3h (OlMIPl). 

Characteristic H NMR data of (4a/ ,55)- and (4n5,5R)-2-substituted 5- [A-(/e/ /-butoxycarbonyl)-L-tryptophyl]amino perhydropyrido[l,2-c]pyri-midine-l,3-diones were tabulated (01JMC2219). C CPMASS NMR data of 4-(4-methoxyphenyl)perhydropyrido[l,2-c]pyrimidine were reported (00JST73). C NMR data were reported for eight 4-aryl-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidin-l,3-diones in the solid state and in CDCI3 solution (00JPO213). The structure of 4-aryl-3,4-dihydro-2//-pyrido [l,2-c]pyrimidine-l,3-diones and their 2,3,5,6,7,8-hexahydro derivatives were characterized by H and C NMR data (99JHC389). Conformational analysis of 6-methyl-2,3,4,6,7,ll/)-hexahydro-l//-pyrimido[6,l-n]isoquino-lin-2-ones 138 and 139 were carried out by H and C NMR studies (97LA1165). 

Because free or esterified imidazole(4,5)-acetates 745 are currently accessible only via a rather tedious multistep synthesis via (4,5)hydroxymethylimidazole [224— 226], it seemed obvious to react amidines such as isobutyraminidine-HCl 742 with commercially available methyl or ethyl 4-chloroacetoacetates 743a, b to obtain 745 directly in one step. Because of the low reactivity of the 4-chlorine in 743, however, reaction of 743, e.g. with isobutyramidine-HCl 742 in the presence of sodium methylate in methanol, affords exclusively 2-isopropyl-6-chloromethyl-pyri-midin-4-one 744 [227], whereas treatment of 743b with NaOEt in EtOH gives, in the absence of amidines, 2,5-bis(ethoxycarbonyl)cyclohexane-l,4-dione in nearly quantitative yield [228, 229]. 

CB3377 70GEP1904894). 4-Amino-6-mercaptopyrazolo[3,4-[Pg.338]

Certain types of pyrido[l,2-a]pyrimidines have aroused much interest owing to their valuable pharmacological properties. They are also used as synthetic intermediates or as additives to photographic materials and dyes. In the following sections the syntheses, reactions, physicochemical properties, and briefly the utilization of the pyrido[l,2-ci]pyrimidines are discussed. Within the individual sections the pyrido[l,2-ti]pyrimidinium salts, followed by the 2-oxo-2//-pyrido[l,2-a]pyrimidines, 4-oxo-4H-p3 rido[l,2-a]pyri-midines, 3,4-dihydro-2/7-pyrido[l,2- ]pyrimidines, 2-oxo-3,4-dihydro-2H-and 4-oxo-2,3-dihydro-47/-pyrido[l,2-a]pyrimidines, and finally miscellaneous pyrido[l,2- (]pyrimidines are dealt with. 

When the 5-phenyl derivative of 43 was used, a mixture of 3-(2-phenyl-2-chloroethyl)- and 3-(2-phenylvinyl)-8-methyl-4-oxo-4H-pyrido[l,2-a]pyri-midines was obtained.49 Depending on the conditions, reaction of 2-aminopyridines with 2-acetyl-4-chloromethylbutyrolactone (47) led to a variety of bicyclic products (48-54) (Scheme 2)49,83 Reaction of 2-aminopyridines with the acid chloride (55) yielded 4-oxo-4H-pyrido[l,2-a]pyrimidines (56) and traces of the amides of type 57. From 2-amino-6-methyl-pyridine, only the amide (57 R = 6-Me) was formed.86... 

Stockelmann et al. reacted 2-amino-3-methylpyridine and 2-amino-4-methylpyridine with diketene in water. The 2-oxo-2//-pyrido[l,2-fl]pyri-midine structure was assigned to the products, reportedly obtained in 90 and 97"0 yields.92 Kato et al. 9 and Yale et al45 subsequently demonstrated that the products were 4-oxo-4//-pyrido[l,2- ]pyrimidines and the yields were not higher than 16 . 

Thermal cyclization of the isopropylidene ester of the malonates (70) was accompanied by decarboxylation at position 3, whereby 4-oxo-4H-pyrido-[l,2-fl]pyrimidines (74 R1 = H) were obtained.79,142,143 When the cyclization was performed in phosphoryl chloride-polyphosphoric acid and the reaction mixture was treated with alcohol, 4-oxo-4H-pyrido[l,2-a]pyri-midine-3-carboxylic acid esters were isolated.151 Treatment of the reaction mixture with water gave carboxylic acids. 

If the reaction of 9-halo-4-oxo-6,7,8,9-tetrahydro-4tf-pyrido[l,2-a]pyri-midines and amines was carried out in the absence of air, the 9-amino-4-oxo-6,7,8,9-tetrahydro-4if-pyrido[l,2-a]pyrimidines were isolated, which could be oxidized by air to the 6,7-dihydro analogs.308 The latter were directly prepared from 9,9-dihalo-4-oxo-6,7,8,9-tetrahydro-322 or 9-hydroxy-4-oxo-6,7-dihydro-4A/-pyrido[l,2-a] pyrimidines308 with amines. 

Several novel IOji bicyclic imidazoles (63 or 65), obtained from polysubstituted imidazoles, were reported during this period. The first synthesis of an imidazo[4 ,5 4,5]thieno[3,2-d]pyri-midine commences with l-benzyl-2-(methylthio)-4-bromo-5-cyanoimidazole (62) [95TL12807]. Sequential metallation, sulfurization, S-alkyiation, and Thorpe cyclization of 62 afforded the thienoimidazole intermediate 63. Precursor 62 was obtained from 1 -benzyl-2,4,5-tribromoimida-zole in a series of metallation-electrophile trapping protocols. Nitroimidazo[l,5-a]imidazoles (65) were readily obtained from l-(acylmethyl)-2-methyl-4-nitro-5-bromoimidazoles (64) by sequential amination and cyclization [94KGS490]. 

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