2.4.6- Triaminopyrimidines

The reaction of 6-amino-5-(l,2-diethoxycarbonylhydrazino)pyrimidines with enamines represents another convenient method for the preparation of pteridines. Fusion of 5-(l,2-diethoxycarbonylhydrazino)-2,4,6-triaminopyrimidine (281) with an excess of mor-pholinocyclohexene leads to 2,4-diaminotetrahydrobenzo[g]pteridine, and with the morpholinoenamine (282) from 17/3-hydroxy-5a-androstan-3-one regioselective condensation to the fused pteridine (283) takes place in almost quantitative yield (equation 101) (71CC83). 6-Amino-5-nitroso- and 6-amino-5-phenylazo-pyrimidines react similarly, imitating the Timmis-type reaction (72CPB1428). 

The reaction involves an electrophilic attack into the 5-position of the pyrimidine ring and thus only those pyrimidines that are activated toward electrophilic substitution by the presence of electron-donating substituents at the 2- and 4-positions undergo cyclization. 2,4,6-Triaminopyrimidine, 6-aminouracil, 6-amino-2-thiouracil, 4-amino-2,4 dimercaptopyrimidine, 2,4-diaminopyrimidin-6(l/I)-one, and various 4-amino-vV-alkyl and aryl pyriinidones have all been converted into pyrido[2,3-[Pg.160]

An interesting variation of this procedure relies upon the formation of malondialdehyde precursors in situ. Vinylogs of Vilsmeier-Haack intermediates (60), formed from dimethylaminoacroleins (59) and phosgene, undergo reaction with 2,4,6-triaminopyrimidine to yield 6-alkyl- and 6-aryl-substitutcd 2,4-diaminopyrido[2,3-d]-pyri-midines (61). Dimethylaminoacroleins were found to be unsatisfactory. ... 

Several studies deal with the reactivity of 2,4-disubstituted-6-aminopyrimidines, which have competing sites for ring formation with 1,3-biselectrophiles. Treatment of 2,4,6-triaminopyrimidine with ethyl acetoacetate in acetic acid formed the pyrimido[l,6-tf]pyrimidin-4-one 216, while the expected pyrido[2,3-r/]pyrimidin-7-one 217 was obtained under thermal conditions (Scheme 34) <1999JOC634>. 

The angularly condensed pyrimido[l,6- ]quinazoline 223 was prepared from [3+3] atom fragments by reacting 2,4,6-triaminopyrimidine and ethyl 2-oxo-cyclohexane-l-carboxylate under acidic conditions. The reaction also gave rise to the isomeric linear N-bridgehead tricycle, 224. The expected C-annelated product 225 was obtained under thermal conditions (Scheme 36) <1999JOC634>. 

In 2,4,6-triaminopyrimidine there are two equivalent ring nitrogen atoms (N-1 and N-3), both in Oi-positions to an amino-group and... 

Chemists at Los Alamos National Laboratory synthesized a series of picrylamino-substimted pyrimidines as part of a research effort to And new thermally stable explosives. The pyrimidine-based explosive (187) is synthesized via the reaction of 2,4,6-triaminopyrimidine with picryl fluoride followed by subsequent nitration with nitric acid." ... 

Hydrolysis of pyrimidinamines generally requires more vigorous conditions, although selective hydrolysis can often be achieved. Thus, the acid-catalyzed hydrolysis of 2,4,6-triaminopyrimidine 170 occurred in the 2-position to give 4,6-diamino-2(l//)-pyrimidinone 171 <2001JOC192>. Examples of selective diazotization of diamines are also known <2005JOC1612>. 

An improved synthesis of substituted pyrido[2,3-, pyrimidine-2,4-diamines 477-482 can be carried out by cycloaddition of 2,4,6-triaminopyrimidine 466 with the 1,3-biselectrophiles 467-471 via intermediates 472-476 (Scheme 19) <1994AP221>. 

The pyrido[2,3-, pyrimidines 560 and 562 were prepared as analogues of the multitargeted antifolate (MTA) by the reaction of /3-keto ester 558 with either 2,4-diamino-6(l//)pyrimidinone 490 or 2,4,6-triaminopyrimidine 466, followed by saponification of the resulted glutamate products 559 and 561, respectively (Scheme 25) <1997H(45)2229>. 

The thermal cyclization reaction of 2,4,6-triaminopyrimidine 466 with ethyl 2-cyclohexanonecarboxylate 588 in PhgO at 190 °C gave the tetrahydropyrimido[4,5-r-]isoquinolin-6(5//)-one 589 as the sole product (Equation 48) <1999JOC634>. 

Considering tridentate sites, 2,6-diaminopyridine and uracil are complementary single site groups (see Sections 9.4.2 and 9.4.3 below). On the other hand barbituric acid (BA) and 2,4,6-triaminopyrimidine (TAP) or -triazine (TAT) are Janus molecules containing two identical recognition sites while 168 is plerotopic by virtue of its two complementary sites (see Section 9.4.4). 

Fig. 37. Self-assembly of either a supramolecular ribbon (top) or a supramolecular macrocycle (bottom) from barbituric acid and 2,4,6-triaminopyrimidine units [9.122].

Triaminopyrimidine and barbituric acid derivatives are complementary components presenting the required features, since they should be able to form two arrays of three hydrogen bonds with each other. However, as pointed out above, based solely on hydrogen bonding recognition, their association could yield either a linear or a macrocyclic supramolecular structure (Section 9.4.2 Figure 37). 

Reaction of ethyl a-(arylmethyl)acetoacetate with 2,4,6-triaminopyrimidine gave 7-pyrido[2,3-rf]pyrimidinones <85USP4512992,88EUP279565). Reactions of glycopyranosylaminopyrimidinones with malonic acids in Ac20 afforded the derivatives (343) <91M255>. 

Fig. 25 DDD-AAA and ADA-DAD interactions in tapes formed from 1-(4-carboxybutyl)-1,3,5-triazine-2,4,6-trione with 5-(2-aminoethyl)-2,4,6-triaminopyrimidine [198]...

In recent years, a considerable amount of attention has been focussed on the derivatization of the pyrimidine core structure on resins. Usually, the sequential substitution of the pyrimidine template on a resin with various amines provides a diverse set of 2,4,6-triaminopyrimidines. Synthetic strategies leading to pyrimidines with one [136], two [137,138], and three diversity points have been reported [139-141]. 

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