Uracil, amino

Among various pyrimidines tested in vitro as inhibitors of the active transport of uracil across the rat intestinal wall, strong inhibition was seen with 5-amino-uracil, 5-fluorouracil, 5-bromouracil and thymine [398]. 

A phosphorylase from Escherichia coli has been purified it is specific for 2-deoxy-D-ribosyl phosphate, but can use uracil, 2-thiouracil, 5-amino-uracil, 5-bromouracil, and 2-thiothymine as a pyrimidine. Deaminases of adenosine, 2-deoxyadenosine, cytidine, and 2-deoxycytidine have been detected in Escherichia coli. 

Preparation of 5-[bis(2-Hydroxyethyl)AminoJUracil 20 grams (0.157 mol) of 5-amino-uracil was mixed with 350 ml of water, 23 ml of glacial acetic acid, and 160 ml of ethylene oxide In a one-llter flask immersed in an ice bath. The reaction mixture was stirred and allowed to come to room temperature slowly (as the ice melted), and stirring was continued for two days. A clear solution resulted to which was added 250 ml of water and 60 grams of Dowex-50 in the acid form. The mixture was stirred for 15 minutes, and the resin was collected on a filter. It was washed with water and the crude 5-(bis(2-hydroxy-ethyl)amino] uracil was eluted with a 10% aqueous solution of ammonium hydroxide. 

The 5-amino uracil interacts with nitrous acid (generated from sodium nitrite and hydrochloric acid) at 0-5°C to produce one mole of 5-diazouracil and two moles of water. 

Diazotize the 5-amino uracil (1) by the gradual addition of sodium nitrite solution (2) in small quantum (2 ml) at a time in intervals with vigorous stirring with a glass rod or on a magnetic stirrer. Ample care must be taken so that the temperature of the reaction mixture does not rise beyond 10°C. 

Amino-l,3-dimethyl-5-nitrosouracil (270), reported last year as a highly versatile precursor for the purine and pteridine ring systems, has again found use (Scheme 63) in a new synthesis of 6-hydroxy-pteridines (271). Photo-decomposition of 6-azido-l,3-dimethyluracil as a solution in a secondary or primary amine has been used as a convenient method of preparing 6-alkylamino-5-amino-uracils. The procedure has now been extended ... 

In the case of the 2-dimethylamino- (or 2-amino-)methylene derivatives, the products were at first thought to be pyrimido[4,5-c]isoquinolines (267), but later work with 6-(N-substituted amino)uracils assigned the structures of the products (268) as belonging to the isomeric pyrimido[4,5-f>]quinoline system (74CB2537), in agreement with the regioselection rules above. 

Undissolved substances were removed by filtration and the filtrate was concentrated on a steam bath to a volume of about 125 ml and cooled to effect crystallization. After 20 hours at room temperature the crystals that had formed were recovered, washed with isopropyl alcohol, and dried, yielding 15.61 grams (46.2%) of crystalline 5-[bis(2-hydroxy-ethyl)amino] uracil having a MP of 157° to 163°C. An analytical sample, obtained by several recrystallizations from isopropyl alcohol, melted at 166° to 168°C. 

The product was recrystallized by dissolving in a minimum of hot methanol and adding water until the solution became cloudy 2.25 grams of 5-[bis(2-chloroethyl)amino] uracil was recovered after cooling the mixture to 4°C for 16 hours (MP 200° to 205°C). A small sample was recrystallized again, and it melted at 198° to 204°C. 

Chemical Name 1,3-Dimethyl-4-[7-[4-(o-methoxyphenyl)piperazinyl-(1)] -propyl-amino] -uracil... 

The 9-methylsulfonyl-pyrimido[l,6-tf]pyrimidin-6,8-dione 210 was obtained during attempted mesylation of the 6-[(3-hydroxypropyl)amino]uracil 209 (Equation 25). The methanesulfonyl group of 209 was removed by reduction with Raney Ni to yield 68 <1999JHC453>. 

Electron-rich 6-[(dimethyl(amino)methylene)amino uracil 82 underwent [4+2] cycloaddition reactions with various in situ generated glyoxylate imine and imine oxides to afford novel pyrinhdo[4,5-J]pyrimicline derivatives 83-84 after elimination of dimethylamine from the (1 1) cycloadducts and oxidative aromatization. This one-pot procedure yielded excellent yields when carried out in the solid state and under microwave irradiation <06BMCL3537>. 

Cyanoethyl derivatives of 1-alkyl and 1,3-dialkyl-6-amino uracils (LXX) are reported to have activity as anti-ulcer agents. Inhibition of appetite and hypo-cholesterolemic activity are also claimed [437]. 

Reaction of 6-amino-uracil or thiouracil with an arylidene-substituted Meldrum s acid in boiling AcOH afforded the corresponding octahydropyrido[2,3-r/ pyrimidines 506 <1996JHC45>. Similar cyclization using 6-amino-2-meth-oxy or methylthiopyrimidin-4-one derivatives in boiling nitrobenzene led to 507 <1997JHC521>. 

Acetamido—6-amino uracil or 5-Acetamino 6 amino 2,4 dioxy-pyrimidine, C6HgN40g,... 

A new procedure has been developed by Prajapati and co-workers [97] for the synthesis of pyrimido[4,5-rf]pyrimidines 51. The condensation was carried out in the solid state under microwave irradiations by reacting electron-rich 6-[(dimethy-lamino)methylene]amino uracil that undergoes a [4-1-2] cycloaddition reaction with in situ generated glyoxylate imine to provide novel pyrimido[4,5-if]pyrimidines 51 in excellent yields (Scheme 37). 

S-Deazaflavins. A new synthesis of 5-deazaflavins (2), in which N5 of a flavin is replaced by CH, involves oxidative cyclization of 5-benzylidene-6-(N-substituted amino)uracils (1) with DAD at 150°. 

N,N-BIS(2-CHLOROETHYL)AMINOURACIL CB-4835 CHLORETHAMINACIL DEMETHYIDOPAN DESMETHYLDOPAN 5-pi-(P-CHLOROETHYL)-AMINO)URACIL 5-pi-2-CHLOROETHYL)AMINO-URACIL 2,6-DIHYDROXY-5-BIS(2-CHLOROETHYL)-AMINOPYRAMIDINE ENT 50,439 NCI-C04820 NORDOPAN NSC-34462 RCRA WASTE NUMBER U237 OSK-19849 U-8344 URACILLOST URACILMOSTAZA URACIL MUSTARD URAMUSTIN... 

BIS(2-CHLOROETHYL)AMINO)URACIL see BIA250 5-N,N-BIS(2-CHLOROETHYL)AMINOURACILsee BIA250... 

Reaction with isocyanates and isopropyl-sulfonyl-chloride, via the ura-cil-enamino esters, easily gives pyrimido[4,5-Thermal cyclization of 6-amino-uracil-5-thiocarboxamides, prepared by reacting 6-aminouracils with isothiocyanates yields pyrimido[4,5-[Pg.163]

The dimethylformamide/phosphoryl chloride reagent has been used to cyclize 6-(acylamino)-uracils by introducing the missing carbon unit.201 Thus, treating l,3-dimethyl-6-[(cyanoacetyl)amino]uracil with dimethylformamide/phosphoryl chloride yields 1,3-dimethyl-5-chloropyrido[2,3-rf]pyrimidine-2,4,7(l//,3f/,8//)-trione (8, R = H). 

Other typical C3 components are 2-aryl-3-(dimethylamino)acryladehyde.257 3-(methylamino)-bul-3-en-2-one, A-unsubstituted 2-(aminomethylene)cycloalkanones,258 or l-phenyl-3-pipe-ridinoprop-2-en-l-one,259 all of which can be regarded as vinylogous amides. With 4-amino-uracils in dilute acetic acid at reflux temperature, pyrido[2,3-d]pyrimidine-2,4(1 f/,3//)-diones 26 are obtained. According to the position of substituenls in Ihese cases, the amino group of the uracil reacts with the /5-vinyl carbon, followed by cyclization through electrophilic attack of the aldehyde or ketone carbonyl.257,259... 

Solvent-free condensation of malonic acid or cyanoacetic acid and ureas in the presence of acetic anhydride under MW irradiation conditions affords functionalized uracil derivatives such as 6-hydroxy or 6-amino uracils in high to excellent yields (Scheme 8.76) [188]. 

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