Pyrimidines, 4-fluoro-, synthesis

Pyrimidine, 2-ethyl-1,4,5,6-tetrahydro-synthesis, 3, 108 Pyrimidine, 5-formyl-2-methyl-in thiamin biosynthesis, 1, 99 Pyrimidine, fluoro-synthesis, 3, 140 Pyrimidine, 2-fluoro-,9F NMR, 3, 63 synthesis, 3, 140 Pyrimidine, 4-fluoro-synthesis, 3, 140 Pyrimidine, 6-fluoro-synthesis, 3, 140 Pyrimidine, fluoroalkyl-synthesis, 3, 77... 

Pyrimidine, 4-fluoro-2-isopropyl-synthesis, 3, 140 Pyrimidine, 4-fluoro-2-methoxy-synthesis, 3, 140 Pyrimidine, 4-fluoro-2-methyl-NMR, 3, 63 Pyrimidine, halo-aleoholysis, 3, 100 aminolysis, 3, 99 as antitumour agents, 3, 152 bipyrimidines from, 3, 103 Buseh biaryl synthesis, 3, 103 hydrolysis, 3, 101... 

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

When perfluoro-2-methylpent-2-ene reacts with amidine, the products may be vinylamidine, fluoropyrimidine, or hydroxypyrimidine depending on the reactivity of the amidine and on the presence of a catalyst as well as reaction time. In moderately polar media such as diethyl ether, the initial product is vinylamidine, promoting subsequent cyclization and dehydrofluorination the products of these transformations may be isolated and characterized. Meanwhile, other transformations occur with comparable rates. Therefore, the reaction in diethyl ether may not be used for the synthesis of fluoro-pyrimidines. However, hydroxypyrimidine may be obtained under these conditions with a yield of up to 60%. Analogous results were obtained when the reaction was conducted in Freon-113 (97IZY2024). 

A two-step synthesis of modified 2 -C-nucleoside precursor, ethyl [2-(5-methyl-2,4-dioxo-3,4-dihydro-2i/-pyrimidin-l-yl)-4-hydroxyl-5-hydroxymethyltetra-hydrofuran-3-yl]fluoro-acetate 172, from protected glycal 170 and xanthate has been developed following the same idea, and a diastereomeric 1 1 mixture of 2,3-trans product 171 was obtained in 57% yield (O Scheme 46). The use of triethylborane as a free-radical initiator was less successful and a longer reaction time was also required. Interestingly, introducing th)miine at C-1 in the presence of silver triflate at 0°C was highly stereoselective, and only a C, C2-trans linked product was detected. 

Synthesis of 2 -Deoxy-2 -oc-fluoro Pyrimidine Nucleosides via Cleavage of Cyclonucleosides... 

The synthesis of 2 -deoxy-2 -a-fluoro purine nucleosides via cleavage of purine O-cyclo-nucleosides (see Scheme 7.2) has not been reported, presumably for the following reasons [18] (i) the synthesis of purine O-cyclonucleosides is not so easy as that of pyrimidine O-cyclonucleosides (ii) the glycosyl bond of purine nucleosides is rather unstable under severe reaction conditions such as the use of HF and (iii) it is not easy to remove the... 

Brothwick, A. D., Evans, D. N., Kirk, B. E., et al. (1990) Fluoro carbocyclic nucleosides synthesis and antiviral activity of 2 -and 6 -(luoro carbocyclic pyrimidine nucleosides including carbocyclic l-(2-deoxy-2-fluoro-P-d-arabinofuranosyl)-5-methyluracil and carbocyclic l-(2 -deoxy-2-fluoro-P-d-arabinofuranosyl)5-iodouracil. J. Med. Chem., 33, 179-186. 

Wnuk, S.F., Bergolla, L.A., and Garcia, P.L, Jr., Studies toward the synthesis of a-fluorinated phosphonates via tin-mediated cleavage of a-fluoro-a-(pyrimidin-2-ylsulfonyl)alkylphosphonates. Intramolecular cyclization of the a-phosphonyl radicals, J. Org. Chem., 67, 3065, 2002. 

The limited therapeutic activity of the fluorinated pyrimidines 5-fluorouracil (FU) and 5-fluoro-2 -deoxyuridine (FUdR) in certain forms of adenocarcinoma, principally of the digestive tract, have led to the synthesis of a variety of analogues. Dinucleoside phosphates containing FU... 

---