An Efficient Synthesis of 7,8‐Dihydropyrimido[5,4‐d]pyrimidines

Abstract

Keywords: Cyanopurines / Amines / Rearrangement / Pyrimido [5,4-d]pyrimidines 7,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 Mild Approach to the Synthesis of 4‐Amino‐8‐(arylamino)pyrimido[5,4‐d]pyrimidine 3‐Oxides

“…Our studies [21,34] showed that nucleophilic attack of the amine to C8 of the purine ring was the first step of the cascade process leading to the formation of pyrimido-pyrimidine 2 through an ANRORC type mechanism (Scheme 1). Compounds 2 were isolated in very good yield, although in some cases the rearrangement product 3 could also be identified as a minor product.…”

“…[12,16,17] The 6-cyanopurines were also used as precursors of the pyrimido [5,4-d]pyrimidines by reaction with an amine. [3,4,6,[18][19][20][21] To the best of our knowledge, pyrimido [5,4-d]pyrimidine N-oxides were never reported in the literature. However, pyrimidine N-oxides are known.…”

6-Carbohydrazonamidepurines: Convenient Precursors for 4,8-Disubstituted Pyrimido[5,4-d]pyrimidines

“…6-Cyanopurines 1 had been previously used to generate 6-imidatopurines 6, 12 and reaction of these compounds with hydrazides was carried out in the presence of acid catalysis, aiming to prepare the 6-amidinopurines 4. Previous results on the reactivity of the purine ring, under basic conditions and in the presence of nucleophiles, indicated that attack on C8 was the major pathway, [8][9][10] leading to pyrimidopyrimidines 2. The use of a catalytic amount of sulfuric acid, when a suspension of compound 6a in dimethylsulfoxide was combined with acetic hydrazide 7a, prevented the competitive formation of product 2.…”

“…7 This approach has been used in our group for the efficient synthesis of compounds 2 (Scheme 1). 4,[8][9][10] According to the literature, structure 2 can be used to generate the aromatic analogue 3 by Dimroth rearrangement, in the presence of acid or base catalysis. 11 Furthermore, our studies on the reactivity of the pyrimidopyrimidine derivatives 2 (R 2 = OBn) have proved that the conversion of 2 (R 2 = OBn) into 3 (R 2 = OBn) occurs efficiently under acid conditions although other products may also be formed (Scheme 1).…”

Bicyclic 6 + 6 systems: the chemistry of pyrimido[4,5-d]pyrimidines and pyrimido[5,4-d]pyrimidines

“…80 Furthermore, 9-substituted-9H-purine-6-carbonitriles 167 were used as synthetic intermediates for the synthesis of pyrimido [5,4-d]pyrimidine analogs 168 by reaction with various amines through ring transformations (Scheme 41). 14,24,[81][82][83][84][85][86][87][88][89] A series of pyrimido [5,4-d]pyrimidines 170 were prepared by reaction of 9-substituted-9H-purine-6-carbonitriles (167) with various hydrazides 169 by treatment in DMSO and water using catalytic DBU. Compound 170d was obtained by the reaction of 9-aryl-9H-purine-6-carbonitriles 167 with acetohydrazide (169c) in acetonitrile instead of DMSO and compounds 170k and 170o were prepared in ethanol (Scheme 42).…”