With Formamide or Other Amides

The first use of formamide to convert an o-aminoamide to an annelated pyrimidin-4-one seems to have been Price and Curtin s synthesis of pyrido[3,2-d]pyrimidin-4-one (see 6) from 3-aminopyridine-2-carboxam-ide.216 This reaction has been used mainly on 7r-deficient starting materials for which it is more efficient than formic add and, on occasion, triethyl 

The formamide reaction has been successfully used to convert a 2-amino-pyridine-3-carboxamide to pyrido[2,3-d]pyrimidin-4-ones (see 3)220 3-aminopyrazole-4-carboxamide (see 15) to pyrazolo[3,4-rf ] pyrimidin-4-ones (see 16)118 4-aminopyrazole-3-carboxamide to pyrazolo[4,3-d]pyrimi-din-7-ones (see 17)221 many 4-amino-1,2,3-triazole-5-carboxamides (see 20) to 8-azapurin-6-ones (see 21)157,217-222—226 and 4-aminoimidazole-5-car-boxamides (see 18) to purin-6-ones (see 19).124-202-227 228 Secondary amines are suitable starting materials, as in the conversion of 4-amino-l,2,3-triazole-5-(jV-methyl)carboxamide and its 3-benzyl63 and 

4- Methylamino-l,2,3-triazole-5-carboxamide and its 3-benzyl derivative (see 20) performed much better in acidified triethyl orthoformate.64 

Dimethylformamide diethylacetal converted 2-benzylaminopyrazine-3-carboxamide to l-benzylpteridin-4-one (see 10) in good yield after 1 hr of refluxing, although this pyrazine had resisted the more common cyclizing agents.230 

Except for trifluoroacetamide, which gave an excellent yield of 2-trifluoro-methylpurin-6-one (see 19) when refluxed for 2 hr with 4-aminoimidazole-5-carboxamide,231 the higher amides lack the reactivity of formamide. 

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