Pyrimidin-2 -ones sodium borohydride

Perhaps the most useful part of the reported synthesis is the facile preparation of (—)-pyrimidoblamic acid (12 Scheme 3). A key to this synthesis is the preparation of the fully substituted pyrimidine 8. This was done by a one-pot inverse electron demand Diels-Alder reaction between the symmetrical triazine 7 and prop-1-ene-1,1-diamine hydrochloride, followed by loss of ammonia, tautomerization, and loss of ethyl cyanoformate through a retro-Diels-Alder reaction. Selective low-temperature reduction of the more electrophilic C2 ester using sodium borohydride afforded 9, the aldehyde derivative of which was condensed with 7V -Boc-protected (3-aminoalaninamide to give the imine 10. Addition of the optically active A-acyloxazolidinone as its stannous Z-enolate provided almost exclusively the desired anti-addition product 11, which was converted into (—)-pyrimidoblamic acid (12). Importantly, this synthesis confirmed Umezawa s assignment of absolute configuration at the benzylic center. 

Reduction of 6,7,8,9-tetrahydro-4//-pyrido[l,2-a]pyrimidin-4-ones 341 and their quaternary salts 343 with sodium borohydride in water and methanol yielded the thermodynamically stable epimer 342 of 1,6,7,8,9,9a-hexahydro-4//-pyrido[l, 2-n]pyrimidin-4-ones (83SZP635100 85JOC2918),... 

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. 

Oxo-4//-pyrido[l,2-a]pyrimidine-7-carboxylates 500 were obtained when 7-iodo-4T/-pyrido[ 1,2-a]pyrimidines 499 reacted with carbon monoxide in the presence of bis(triphenylphosphine)palladium(II) chloride catalyst and triethylamine (Scheme 29) (94MI2). From 7-iodo derivatives 499, 7-vinyl derivatives 501 and 7-(l-ethoxyvinyl) derivatives 502 were prepared with vinyltributyltin in the presence of Pd(PPh3)4 and with (1-ethoxy-vinyl)tributyltin in the presence of bis(triphenylphosphine)palladium(II) chloride catalyst, respectively, in toluene at 80°C. 7-(l-Ethoxy vinyl)pyr-ido[l, 2-a]pyrimidin-4-ones 502 were hydrolyzed to yield 7-acetyl derivatives 503. The acetyl group of compounds 503 was reduced with sodium borohydride in the presence of cerium(III) chloride in ethanol to give 7-(1 -hydroxyethyl)pyridopyrimidin-4-ones 504. 

Dihydrothieno[3,4-d]pyrimidin-3(l//)-ones 337 were synthesized by a four-step reaction sequence starting from carbamates 310. The latter were selectively reduced with lithium aluminum hydride and then oxidized with activated manganese(IV) oxide to give aldehydes 334 in one-pot. Condensation of compounds 334 with ethanolamine in refluxing ethanol afforded the Schiff bases 335, which were reduced with sodium borohydride to... 

Both the foregoing photoadducts exhibit three diffusion-controlled polarographic waves in aqueous medium in the pH range 1-12 92). The first two waves are due to successive one-electron additions, followed by the third, a two-electron reduction step. The pH-dependence of the initial one-electron reduction wave was found to be similar to that for pyrimidone-2. Following electrolysis, at the crest of wave I, of either of the photoadducts, the two one-electron waves disappeared and the reduction products exhibited UV absorption spectra with a band at 375 nm. A similar absorption band is exhibited following sodium borohydride reduction of Cyt(5-4)Pyo, leading to a product identified as 5-(4-pyrimidin-2-one)-3,6-dihydrocytosine. Mass spectroscopy revealed that the products of reduction on wave I were dimers consisting of two molecules of reduced photoadducts 92). 

Pyrimidin-2(l//)-ones (85 X = O) and -thiones (85 X = S) on reduction with sodium borohydride afford mixtures of lH-3,4- (86) and l//-3,6-dihydropyrimidinones (87), the product ratios depending on the acidity of the medium, and some further reduction to the fully reduced pyrimidinones may also occur. Similar results are obtained with LAH as the reductant, although l-arylpyrimidine-2-thiones mainly form the corresponding 3,6-dihydropyridine-2-thiones (88), especially if a hydroxy or methoxy group occupies an ortho position in the aryl substituent. This suggests that the group may complex with the reagent and facilitate an intramolecular hydride transfer reaction. L-Selectride reduces N-benzyl-... 

Quaternization of the pyrimidine ring of quinazolines enhances its reactivity toward nucleophiles. This reactivity has been used to advantage for preparing 1,2,3,4-tetrahydro derivatives. Methylation of 4-phenylquinazoline occurred at N-1 and N-3 (7 1) and was the first example in which it was shown that alkylating at two different sites in quinazolines was possible. The l-methyl(and 3-methyl)quinazolinium salt that was formed was reduced with sodium borohydride to l-methyl(and 3-methyl)-4-phenyl-l,2,3,4-tetra-hydroquinazoline. Potassium permanganate oxidized the latter compound to l-methyl-4-phenylquinazolin-2(lH)-one. 

Examples of sodium borohydride reductions of C—N double bonds in the pyrimidine part are the formation of l-isopropyl-4-phenyl-3,4-dihydropyrido[2,3-<7]pyrimidin-2( 1 //)-one (2) from l-isopropyl-4-phenylpyrido[2,3- /]pyrimidin-2(1//)-one (l),73 and of 3-methyl-l-[(3-trifluoro-methyl)phenyl]-1,2-dihydropyrido[2,3-<7]pyrimidin-4(3//)-one (4) from 3-methyl-l-[(3-trifluo-romethyl)phenyl]pyrido[2,3-rf]pyrimidin-4(3//)-one cation (3).413... 

The product of the reaction of sodium or potassium borohydride with substituted pteridines is highly sensitive to the location of the substituent. Thus, Albert and Matsuura151 reported the formation of 2-oxo-l,2,3,4-tetrahydropteridine (152) from the reaction of potassium borohydride with pteridin-2-one (151). This appears to be the only example of attack of the pyrimidine ring of pteridines by complex metal hydrides. The same dihydropteridine (152) was formed by reduction of 151 with hydrosulfite ion, and the structure of the product of the latter reaction was elegantly proved using deuterium... 

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