4,5-Diaminopyrimidines

Pyrimidinesulfinic acids are so rare that few reactions are recorded but pyrimidinesul-fonic acids are known to undergo a variety of reactions. The typical sulfinic acid (379 R = SO2H) reacts with ethanolic hydrogen chloride to give 5,6-diaminopyrimidin-4(3ff)-one... 

Because 5-nitrosopyrimidines are so accessible, their oxidation to the corresponding nitropyrimidines is of considerable potential use. Thus, 4,6-diaminopyrimidin-2(l//)-one... 

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. 

A novel type of ring closure is the reaction of 6-amino-5-dichloroacetylaminopyrimidines (285) with sulfur and morpholine under the conditions of a Kindler reaction (B-64MI21605). 7-Morpholinopteridin-6-ones (287) are formed, either via thiooxamide derivatives (286) or via corresponding 7,8-dihydropteridines (284 equation 102). Chloral hydrate also reacts with 2-substituted 5,6-diaminopyrimidin-4-ones to form pteridin-6-ones (56JCS3311, 64JCS565) by a so far unknown mechanism. 

Chloro-2,6-diaminopyrimidine (2,4-diamino-6-chloropyrimidine) [156-83-2] M 144.6, m 198 , 199-202 , pK 3.57. Purified by recrystn from boiling H2O (charcoal) as needles also crystallises from Me2CO. [Biittner Chem Ber 36 2232 1903 Roth J Am Chem Soc 72 1914 1950 UV J Chem Soc 3172 1962.]... 

The mechanism of cyclization of diaminopyrimidines by nitrous acid appears not to have been studied in detail. For the preparative procedure an aqueous solution of alkaline nitrite is treated with the diaminopyrimidine either in the form of a salt or with simultaneous addition of hydrochloric or acetic acid. The first phase of the reaction is usually carried out at 0°C, in some cases the reaction being terminated by heating to 50-60°C. With diaminopyrimidines which are sparingly soluble in water, the reaction was carried out in an organic solvent using amylnitrite. Excess nitrous acid can possibly attack the amino groups present. This was employed in some cases for the preparation of the hydroxy derivatives. ... 

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]

G. H. Hitchings and his co-workers have made a comprehensive studyof antifolic acid activity in 2,4-diaminopyrimidines. They have demonstrated that very many such compounds, both simple and fused, show such activity. In the course ofthis work some pyrido[3,2-d]-pyrimidines and a large number of pyrido[2,3-d]pyrimidinesi ... 

The activating effect of the phenylazo group in the reaction of 6-chloro-5-phenylazo-2,4-diaminopyrimidine and its analogs with amines or with dimethylformamide has been noted by Brown. The activating effect in 4-nitroso-, 4-phenylazoxy-, and 4-phenylazo-... 

Two-bond formation through (4+1) atoms heterocyclization of 1,6(3,4)-diaminopyrimidines with one carbon (Scheme 5). 

Diaminopyrimidines (22) were also cyclized with cyanogen bromide (90JHC851) or phenyl isothiocyanate (97PHA753) to give the corresponding 2-amino- or 2-anilino-l,2,4-triazolo[l,5-c]pyrimidines 30 and 31 respectively (Scheme 15). 

Diaminopyrimidines fused to a number of heterocycles (35) were also cyclized with one-carbon inserting agents to the corresponding hetero-cyclo-l,2,4-triazolo[l,5-c]pyrimidines 36 (75M1111 81JHC43 97JIC27). 

The finding that 2,4-diaminopyrimidines inhibit the growth of microorganisms by interfering with their utilization of folic acid led to an intensive search for antiinfective agents in this class of heterocyclic compounds. This work led to the develop-... 

Barbituric acid is reacted with phosphorus oxychloride then with 2,4,6-trichloropyrimidine and that product with ammonia to give 4-chloro-2,6-diaminopyrimidine... 

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