Amino-pyrimidines, basicity

The nucleophilicity of amine nitrogens is also differentiated by their environments. In 2,4,5,6-tetraaminopyrimidine the most basic 3-amino group can be selectively converted to a Schiff base. It is meta to both pyrimidine nitrogens and does not form a tautomeric imine as do the ortho- and /xira-amino groups. This factor is the basis of the commercial synthesis of triamterene. 

Reaction of 2-[A -(2-alkenyl)amino]-3-formyl-4/f-pyrido[l, 2-n]pyrimidin-4-ones 235 with HONH2 HCl under both acidic and basic conditions (in the absence or in the presence of NEts) gave tetracyclic derivatives 236 in good yields. Higher yields were achieved in the presence of NEts (96T887). 

Labeled compounds have also been produced by the hydrolysis of reduced pyrimidine derivatives, and thus the basic hydrolysis of 5,5,6,6-tetradeuterouracil 547 (R = D) gave 2,2,3,3-tetradeutero-/5-alanine 548 (R=D) in 50% yield <2001JLR7>. 5,6,6-Trideuterothymine 547 (R = Me) behaved similarly to give 2,3,3-trideutero-3-amino-2-methylpropanoic acid 548 (R = Me), also in 50% yield <2001JLR7>. Similar procedures have been performed with tritiated uracil derivatives <2002MI295>. 

For the regulation of metabolic pathways metabolites are often used which are a product of that pathway. The basic strategy for the regulation is exemplified in the mechanisms employed in the biosynthetic and degradation pathways of amino acids, purines, pyrimidines, as well as in glycolysis. In most cases a metabolite (or similar molecule) of the pathway is utilized as the effector for the activation or inhibition of enzymes in that pathway. 

The enaminonitriles 55a and c react with 12 in refluxing pyridine to give 59a and b. In contrast, 12 and 55b react in acetic acid to give the oxa-zinopyrazolo[l,5-a]pyrimidines 60. It is assumed that the amino function in 12 adds to the activated double bond in 55 to yield the intermediate adduct 56, which loses chloroform to yield 57. This cyclizes under basic conditions to yield 59a and b. In acetic acid, the 58 that is formed is converted under the reaction conditions to the oxazino[4,5 5,6 ]pyrazolo[I,5-a]pyrimidine derivative 60 (77ZN(B)I478). 

---