Formamide pyrimidine ring

A combination of the preceding type of synthesis and of cyclization of 4-amino-5-arylazopyrimidine can be seen in the novel procedure of Richter and Taylor. Proceeding from phenylazomalonamide-amidine hydrochloride (180), they actually close both rings in this synthesis. The pyrimidine ring (183) is closed by formamide, the triazole (181) one by oxidative cyclization in the presence of cupric sulfate. Both possible sequences of cyclization were used. The synthetic possibilities of this procedure follow from the combination of the two parts. The synthesis was used for 7-substituted 2-phenyl-l,2,3-triazolo[4,5-d]-pyrimidines (184, 185). An analogous procedure was employed to prepare the 7-amino derivatives (188) from phenylazomalondiamidine (186). 

Having a cyano group and an amino group ortho to each other on a ring is another system that has led to the formation of fused pyrimidine ring systems. In this case, an aminopyrimidine is the result. Compound 42 in Scheme 5 is one such structure. Treatment of 42a with formamide leads to the amino derivative 43 <1999PS(155)175>. Alternatively 42b provides 44 after treatment with triethyl orthoformate followed by hydrazine <1999PS(155)175>. 

The 8-methylene carbon atom in 5,6,7,8-tetrahydroquinazoline was activated by the pyrimidine ring, and reacted with formamide and phosphoryl chloride (a Vilsmeier reagent) to form 8-formamidomethylene-5,6,7,8-tetra-hydroquinazoline.197 The latter was also obtained as a by-product in the synthesis of 5,6,7,8-tetrahydroquinazoline from cyclohexanone and trisform-amidomethane.1982-Phenyl-5,6,7,8-tetrahydroquinazoline-4(3//)-thione was synthesized from 1-morpholinocyclohex-l-ene and benzoylisothiocyanate. The thione group underwent the usual metathesis reactions.199 2-Methyl-5,6,7,8-tetrahydroquinazoline-4(3//)-thione was oxidized with potassium permanganate to 2-methyl-4-sulfo-5,6,7,8-tetrahydroquinazoline, which provided 2-methyl-5,6,7,8-tetrahydroquinazolin-4(3//)-one on hydrolysis.145... 

Scheme 28.3.6 shows the synthesis of flufenerim. The pyrimidine ring is formed from a Claisen condensation of methyl 2-fluoropropionate with methyl acetate [65] followed by reaction of the fluoroacetopropionate with ammonia in phosphomo-lybdic acid [66] and cyclization with formamide in the presence of base [67]. 

Section 4.2.1 will be devoted to heterocycles, section 4.2.2 will cover other kinds of protomeric tautomeric equilibria (e.g., enol/ketone, formic acid, formamidine, etc.), and section 4.2.3 will discuss an example of a ring/chain tautomeric equilibrium. The order of presentation will be approximately by increasing molecular weight within each section. A review by Kwiatkowski et al. [267] covers work on formamide, pyridines, pyrimidines, purines, and nucleic... 

A similar route to the i -triazolo[4,5-d]pyrimidine ( 8-azapurine ) ring system has been developed. This involves reaction of 4-amino-l,2,3-triazole-5-carboxamide or its ring iV-alkyl derivatives with formamide (Scheme 46). - 232-234 pyrimidone derivatives thus... 

Ready formation of pyrazolo[3,4-4 pyrimidines from reaction of 5-aminopyrazole -carboxylic acid derivatives is a well-established route to derivatives of this ring system. A recent application is the conversion of 286 into 288 by reaction with formamide and NIS 287 (Equation 40) <2002BML1687>. 

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... 

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