Pyrimidines perhydro

Pyrimidine, 2,2,4,4,6-pentamethyl-2,3,4,5-tetrahydro-conformation, 3, 62 synthesis, 3, 118 Pyrimidine, perhydro-polymers, 1, 313-314 Pyrimidine, phenyl-nitration, 3, 78 Pyrimidine, 4-phenyl-synthesis, 3, 72, 116 Pyrimidine, 5-phenylazo-synthesis, 3, 131 Pyrimidine, 4-phenyI-6-styryl-1-oxide... 

Barbituric acid — see also Pyrimidine-2,4,6-trione, perhydro-acidic pK, 3, 60 bromination, 3, 70 fluorination, 3, 70 structure, 3, 68 tautomerism, 2, 27 in thermography, 1, 392 Barbituric acid, iV-alkyl-chlorination, 3, 70 Barbituric acid, 5-aminomethylene-synthesis, 3, 524 Barbituric acid, 5-arylidene-pyridopyrimidines from, 3, 227 Barbituric acid, 1,3-dicyclohexyl-synthesis, 3, 113 Barbituric acid, 2-thio-sensitizing dye... 

Hydrolysis of 3-[(2,6-dimethoxy-4-pyrimidinyl)hydroxymethyl]perhydro-pyrido[l,2-c]pyrimidin-l-iminium salts 174-177 in boiling cone. HCl afforded the appropriate 3-[(2-hydroxy-6-oxo-l,6-dihydropyrimidin-4-yl) hydroxymethyl] derivative (98TL7021, 00JA5017). 

However, in many other series results have been obtained that are compatible with those from other methods and that gave the dipole-moment method an appearance of general reliability now known to be unjustified. Such compatible results include spiropiperidines (Section III,A,4), tropanes (Section III,B,4), 2-alkyltetrahydro-l,2-oxazines (Section III,C,2), perhydro-pyrido[l,2-c][l,3]oxazines (Section III,D,IX perhydropyrido[l,2-c][l,3]thi-azines (Section III,D,2), dialkylhexahydropyrimidines and perhydropyrido-[l,2-c]pyrimidines (Section III,D,3), 5-alkyldihydro-l,3,5-dithiazines (Section III,G,3), 3,5-dialkyltetrahydro-l,3,5-thiadiazines (Section III,G,4) and, in part, l,2,4,5-tetraalkylhexahydro-l,2,4,5-tetrazines (Section III,H,4) as well as piperidines, tetrahydro-l,3-oxazines, and tetrahydro-l,3-thiazines containing an N-H group. 

Hydrogenation of 6-methyI-4-oxo-4//-1,6,7,8,9,9a-hexahydropyrido[ 1,2-a]pyrimidine-3-carboxylic ester to the perhydro derivative was performed by catalytic (Pd/C) hydrogenation. The 1-methyl derivative was reduced by sodium borohydride.75133... 

By hydrogenating 2.9-disubstituted 4-oxo-4H-pyrido[l,2-a]pyrimidines or their 6,7,8,9-tetrahydro derivatives over platinum(IV) oxide, Yale and Spitzmiller obtained a mixture of diastereomeric perhydro compounds.58 Separation was not attempted. 

The magnitudes of the coupling frequency of the 1,3-dicarbonyl moiety of 4-oxo-4H-, 6,7,8,9-tetrahydro-, l,6,7,8,9,9a-hexahydro-, and perhydro-4-oxo-4/f-pyrido[l,2-a]pyrimidine-3-carboxylates are characterized by shifts and by the intensity differences of the coupled vibration bands in their IR spectra (92MI11). 

Scheme 3. 15N NMR Data for some tetrahydro-, hexahydro-, and perhydro-4//-pyrido[ 1,2-a]pyrimidin-4-ones...

Perhydropyrido[l,2-a]pyrimidin-4-one 349 was prepared by first reacting pyrido[l,2-a]pyrimidin-4-one 347 with methyl iodide in acetone in a sealed tube at 150°C for 24 hours, then dissolving the evaporated residue in methanol, and treating the methanolic solution with sodium borohydride (81USP4291036). Perhydro derivative 349 was isolated as its hydrochloride salt. The stereochemistry of the product was not determined. 

Perhydro derivatives (270) are prepared from 1-substituted 1,4,5,6-tetrahydro-pyrimidines which form cycloadducts with epoxides (70LA(742)128). 4H-5,6-Dihydro-l,3-oxazines and -thiazines react in the same way to form products of type (270) (66AG(E)875). 

The ring systems reviewed include the perhydropyrazolo[l,2-a]-pyridazines (1), perhydropyrazolo[l,5- ]pyridines (2), perhydro-isoxazolo[2,3-a]pyridines (3), perhydropyrrolo[l, 2-/>]pyridazines(4), perhydro-imidazo[ 1,5-u]pyridines (5), perhydro-oxazolo[3,4-o]pyri-dines (6), perhydrothiazolo[3,4-u]pyridines (7), perhydropyrrolo[l,2-c]pyrimidines (8), perhydropyrrolo[l,2-c][l,3]oxazines (9), perhydro-imidazo[l,2-u]pyridines (10), perhydro-oxazolo[3,2-a]pyridines (11),... 

The 3-imino group of 4-cyano-2-ethyl-3-imino-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidine-l-thione was acylated with phenyl isocyanate (78MI1). The imino group of l-imino-4-cyano-3-methylthio-l//-pyrido[l,2-cjpyrimidine was alkylated and acylated with methyl iodide and acetic anhydride (75YZ13). Reaction of 3-amino-4-phenyl-4-[2-(A, N-di-n-pro-pylamino)ethyl-4,4 a,5,6,7,8-hexahydro-l //-pyrido[l, 2-c ]pyri midin-l-one with acetic anhydride in pyridine and with sodium nitrite in aqueous acetic acid afforded 3-acetamido and perhydro-l,3-dioxo derivatives, respectively (87USP4680295). 

The reactions of 2-piperidineacetamides with aqueous formaldehyde [68BRP1114397 72JCS(P2)1920] or with A, A-dimethylcarboxamide dialkyl acetals (84EUP104647 85JMC1285) gave perhydro- or 4,4a,5,6,7,8-hexahydro-3/7-pyrido[l,2-c]pyrimidin-3-ones, respectively. Reaction of 1-chlorocarbonyl-2-[l-cyano-l-phenyl-3- [A,A-di(2-propyl)amino]propyl piperidine with ammonium hydroxide or primary amines at 80°C afforded... 

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