2.4- Diaminopyrimidine, synthesis

Since the structures of the Gabriel-Isay condensation products of 5,6-diaminopyrimidines with unsymmetrical 1,2-dicarbonyl or a-substituted monocarbonyl compounds are always ambiguous, the synthesis of 6- and 7-substituted pteridines by an unambiguous approach was and still is a necessity and an important challenge. 

Roberts et al. (1966) described a similar synthesis cyanoacetaldehyde and guanidine hydrochloride gave 40-80% yields of 2,4-diaminopyrimidine under the conditions of the lagoon model mentioned above. Hydrolysis of diaminopyrimi-dine leads to cytosine, isocytosine and uracil. Thiourea reacts with cyanoacetylene to give 2-thiocytosine however, the yield is considerably lower than with urea or... 

Dealing with the synthesis of dihydropyridopyrimidinones, the procedure was quite similar to the precedent, involving 2,6-diaminopyrimidin-4(3//)-one as enaminocarbonyl partner, various 1,3-dicarbonyl derivatives, and either aliphatic or aromatic aldehydes in water under microwave irradiations (Scheme 11). Interestingly, the guanidine system was unreactive, and a library of tri- and tetracyclic dihydropyridopyrimidinone derivatives was chemoselectively synthesized in high yields and short reaction times from this environmentally friendly procedure. 

Table 5 Synthesis of pteridines by Michaei addition of 5,6-diaminopyrimidines (Scheme 16) <1999JHC435>...

Table 6 Pteridine synthesis by imidate condensation with 5,6-diaminopyrimidine (Scheme 18) <2006RJ0136>...

Synthesis of this ring may be achieved by the construction of one of the heterocycles followed by using it as a basis to build the other ring onto it or by the Dimroth rearrangement of l,2,4-triazolo[4,3-a]pyrimidines. 1,2-Diaminopyrimidines are general precursors, and they can be generated from 1-amino or 2-aminopyrimidines. The 3- and 5-amino-l,2,4-triazoles are alternative precursors that can act as a source of three carbons to complete the pyrimidine ring. 

About 6 years later, Broom and Srinivasan [76] described the synthesis of the 5-deaza-5-oxo analogues ((85a) and (85b), respectively) of AP and MTX Scheme 3.17). Beginning with ethyl 4-amino-2-methylthio-5-oxopyrido-[2,3-d]pyrimidine-6-carboxylate (82), readily available in four steps from 2-methylthio-4,6-diaminopyrimidine (81) [77], they prepared the diaminoalcohol (83) in three steps. Conversion of (83) to the bromomethyl compound (84) was followed by reaction with (31) or (35) and saponification to generate the target compounds (85a) and (85b). At about the same time, it was reported that (80a)... 

In the first year of the 20th century, there was a new finding concerning the synthesis of pteridine, known as Gabriel-Coleman synthesis. In this method, pteridine derivatives are generally produced through the condensation of 2,3-diaminopyrimidine 55 with a-diketone (Eq. 5). One century has passed since the development of Gabriel-Coleman synthesis, however, modern synthetic procedures of tetrahydrobiopterin (43) conceptually depend on this synthe-... 

Azine approach. In the cyclization of vicinal diaminopyrimidines either thionyl chloride or sulfinylaniline (64JOC2135) can be used, as for example in the synthesis of (745). 

Moving to fused pyrimidines, Tu and co-workers [96] elaborated a microwave-assisted three-component reaction for the synthesis of 2-amino pyrido[2,3-rf pyr-imidines 47-50. 2,6-Diaminopyrimidin-4-one was reacted without any catalyst with an aldehyde and malononitrile, ethyl cyanoacetate, 2-cyanoacetamide or Meldrum s acid. Importantly, aromatic and aliphatic aldehydes perform equally well in the reaction to give the desired products in good yields (Scheme 36). 

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