Pyrimidines amino groups

The first procedure involved starting with the methyl ketone 996, formation of the enamino ketone 997, and condensation with substituted guanidine derivatives to give the desired products 998, with substituent variation on the pyrimidine amino group. 

Treatment of the symmetrical triaminopyrimidine (50-1) with sulfuryl chloride ties up the two adjacent amines in a thiadiazole ring, protecting those groups from attacks in subsequent reactions. Reaction of the product (50-2) with ortho difluorinated benzylamine (50-3) results in the replacement of the pyrimidine amino group by that in the reagent most hkely by an addition-elimination sequence to afford (50-4). That amino group is then converted to the formamide (50-5) with formic acid. Exposure of the product to Raney nickel leads to a loss of sulfur and the formation of the transient intermediate (50-6). This cyclizes to a purine... 

From purines and pyrimidines In the catabolism of purines ad pyrimidines, amino groups attached to the rings are released as ammonia. 

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. 

A variation of this procedure is used for sulfisomidine because of the different character of the amino group in the 4-position of a pyrimidine ring. Two moles of the sulfonyl chloride are condensed with one mole of 4-amino-2,6-dimethy1pyrimidine in the presence of triethylamine. The resulting bis(acetylsulfanilyl) derivative is readily hydrolyzed to the product. The formation of the bis(acetylsulfanilyl) derivative has also been employed for other heterocycHc amines, eg, for synthesis of sulfathiazole and sulfamoxole (44), but the 1 1 reaction is probably preferable. 

The 3- or 5-aminopyrazoles are the synthons used most frequently. The second heterocyclic ring is created between the amino group and the 1-position (if unsubstituted) or between the amino group and the 4-position. Thus 3-substituted 5-aminopyrazoles react with 1,3-difunctional compounds to afford pyrazolo[l,5-a]pyrimidine derivatives (538) (Table 34). Aminopyrazolinones (R = OH) can be used instead of aminopyrazoles. Similarly 3-aminoin-dazole yields pyrimido[l,2-h]indazoles (539). 

Acid chlorides, acetic anhydride,and formamide have also been used to synthesize pyrido[2,3-d]pyrimidines from 2-ammo-nicotinamides, although in the last case high temperatures were necessary. It is suspected that all the foregoing eyclizations proceed via initial acylation of the 2-amino group to yield an intermediate 2 - amidonicotinamide. 

Ureido and benzamido derivatives have been prepared, and a 6-amino group in a pyrido[3,2-d]pyrimidine can be diazotized and reduced. ... 

The deactivating effects of 2- and -amino groups in pyrimidine provide an interesting comparison. The 2-ethyleneimino group deactivates the 4- and 6-chlorines in 183 toward ethyleneimine in benzene at 50°, while the 4-ethyleneimino group in 184 deactivates the 6- but not the 2-chloro group. However, in contrast, 2-amino-... 

The 0X0 group facilitates reaction relative to H, CH3, or NH2 substituents on pyrimidines in the displacement of mercapto, arylthio, or amino groups by amines. The 2-thioxo group is reactive toward... 

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