Reactions That Give 4-Aminopyrimidines

A. Reactions That Give 4-Aminopyrimidines 1. With Amides, Imidates, or Nitriles... 

The unexpected 8-hydroxymethylhexahydropyrido[2,3-, pyrimidine-6-spiro-l -cyclohexane-2, 4,6 -triones 520 were obtained from microwave-assisted cyclocondensation of equimolar amounts of 6-aminopyrimidin-4-ones 460 and dime-done with a large excess of formaldehyde (37% in water) in the presence of EtsN as a catalyst <2006TL27>. The reaction proceeded via an initial formation of the 2 1 dimedone/formaldehyde adduct 521 that gave intermediate 522 and 523 which could undergo cyclocondensation with excess formaldehyde to give 520 (Equation 42) <2006TL27>. 

One of the first so-called potassium sparing, nonthiazide diuretic agents contains a pterdine nucleus. This is reflected in the use of the pterdine staring material tetra-aminopyrimidine (38-2) in the synthesis. Thus, reaction of benzaldehyde with that polyamine and potassium cyanide leads to the formation of the cyanohydrinlike a-aminonitrile (63-2) from reaction of the most basic amino group. Treatment of the intermediate with a base leads to the addition of the amine to the nitrile to give the dihydropteridine (63-3). Simple exposure to air leads to dehydrogenation and the formation of triamterine (63-4) [65]. 

It is well known that halomethyleneiminium salts, often prepared in situ (see Section 2.1.2.2) react with ammonium salts, primary amines, secondary amides, urea and IV-substituted ureas to afrbrd amidinium salts, from which the free amidines can be obtained by addition of bases. > 4 Some recent results are given below. Dimethylformamide chloride and other 7V,iV-disubstituted formamide chlorides were reacted with acetanilides, chloroacetanilides, 6-aminopenam derivatives, 2-aminopyrimidine, 4-aminouracil, 2-amino-4-chloropyridazine, 2-aminothiazole, 2-aminobenzothiazole and thiobenzamides to give the amidines via the amidinium salts. In the reaction of MA -disubstituted formamide chlorides with thiobenzamides the solvent seems to be decisive for the course of the reaction. In tertiary formamides the thiobenzamides are desulfurized to nitriles, whereas in CHCI3 or CCI4 amidinium salts (296 Scheme 45) are formed. From trimethylsilyl isocyanate and the fluorinated amine (297) the /V-fluorocarbonylamidine (298) is accessible. ... 

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