Premium
An Efficient Synthesis of 7,8‐Dihydropyrimido[5,4‐ d ]pyrimidines
Author(s) -
Carvalho M. Alice,
Esperança Sandra,
Esteves Teresa,
Proença M. Fernanda
Publication year - 2007
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200600883
Subject(s) - chemistry , pyrimidine , tautomer , ring (chemistry) , imidazole , nucleophile , medicinal chemistry , methanol , amination , substituent , intramolecular force , amine gas treating , purine , amidine , hydrazine (antidepressant) , aryl , ethanolamine , stereochemistry , organic chemistry , catalysis , alkyl , chromatography , enzyme
7,8‐Dihydropyrimido[5,4‐ d ]pyrimidines 4 were isolated in very good yields by treatment of 9‐aryl‐6‐cyanopurines 1 with primary amines. Nucleophilic attack of the amine on C8 of the purine ring was followed by ring‐opening of the imidazole unit, and subsequent intramolecular cyclization involving the newly formed amidine group and the cyano substituent in the pyrimidine ring produced the 7,8‐dihydropyrimido[5,4‐ d ]pyrimidine structure 4 . When ammonia was used instead of primary amines, compound 4 rapidly reacted further to afford the more stable pyrimido[5,4‐ d ]pyrimidine 6 as a result of tautomeric equilibration. The aromatic structure 6 was also isolated when purine 1a and an excess of ethanolamine were heated at reflux in methanol, and also whenpurine 1c was combined with an excess of (4‐methoxyphenyl)hydrazine in THF at room temperature in the presence of a catalytic amount of DBU. In both cases the product is formed by a Dimroth rearrangement of the precursor 7,8‐dihydropyrimido[5,4‐ d ]pyrimidine 4 . (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)