1.3- dimethyl-5-fluorouracil

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

Aromatic compounds can participate in both [2+2] and [4+2] photocycloaddition reactions with uracil derivatives to give either benzocyclobutane or ethenoquinazoline (barrelene) derivatives, which can then undergo a number of subsequent photochemical reactions. The products obtained are dependent upon the reaction conditions, and thus the photocycloaddition reaction between naphthalenes 470 and l,3-dimethyl-5-fluorouracil 471 in cyclohexane gave 4a-fluoro-5,10-ethenobenzo[/]quinazolines 472 as products as a result of a [4+2] photocycloaddition (photo-Diels-Alder) reaction <2002TL3113, 2003H(61)377>. 

In some cases, precolumn analyte derivatization is applied in bioanalytical LC-MS. Derivatization of L-368,899 with trifluoroacetic anhydride was performed to eliminate carryover and adsorption effects [8]. Derivatization of 5-fluorouracil with 4-bromomethyl-7-methoxycoumarin [9] and conversion of sampatrilat to its dimethyl ester [10] was performed in order to enhance the ionization efficiency. 

Difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoic acid 4,ll-bis[(2-Aminoethyl)amino]anthra[2,3-b]furan-5,10-diones 4(l-Anilino-podophyllotoxin derivatives 5-Aza-2 -deoxycytidine 5-Bromotetrandrine 5-Cyclohexylindolyl-2 -deoxyribose (non-natural nucleoside) 5 -Fluorosulfonylbenzoyl 5 -adenosine 5-Fluorouracil 5,5-Diphenylbarbituric acid 6-[(2S,4R,6E)-4-Methyl-2-(methylamino)-3-oxo-6-octenoic acid] cyclosporine D (PSC833) 6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid 6-Mercaptopurine 6-Prenylchrysin 6-Thioguanine 6,7-Dimethoxy-... 

Some drags are also substrates, including (+)cz5 -3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one (SM-12502) [427, 428] and tegafnr [429, 430], which is converted to 5-fluorouracil. Halo-... 

In 1990 Tanaka obtained lithiated I,3-diaIkyl-5-fluorouracils 347 [210], which were iodinated with ICl to afford 348. Later lithiated l,3-dimethyl-5-fluorouracils 347 were reacted with hexafluoropropene 320 [211] to form intermediate carbanion 349 giving after fluoride elimination vinylated products 350 as a mixture of E and Z isomers (Scheme 57). 

Syntheses of Fluorouracil prodrugs relied on either chemical modification of 1 or direct fluorination of the corresponding pyrimidine derivatives. In particular, Tegafur (3) was obtained from 1 by reaction with 2,3-dihydrofuran [49-54], 2-chloro- [55, 56], 2-alkoxy- [57], 2-acetoxytetrahydrofuran [58, 59, 300], and 4-tri-methylsilyloxybutyraldehyde dimethyl acetal (48) (Scheme 9) [60]. Alternatively, 3 was prepared via fluorination of compound 49 [61] or ester 50 [62],... 

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