Synthesis of 5-amino-4-(cyanoformimidoyl)-1H-imidazole: a reactive intermediate for the synthesis of 6-carbamoyl-1,2-dihydropurines and 6-carbamoylpurines

Abstract

~~~~~ 5-Amino-4-(cyanoformimidoyl) -1 H-imidazole (3) has been prepared in good yield by the basecatalysed cyclisation of (Z) -N-(2-amino-l,2-dicyanovinyl)formamidine. Compound (3) reacts with ketones, R1COR2 [R' = R2 = Et, Me, Bu, -(CH2)5-, PhCH,; R1 = Me, R2 = Ph] to give 2,2-disubstituted-6-carbamoyl-l,2-dihydropurines as the major products, together with minor amounts of compounds believed to be novel 7-amino-1 -carbamoyl-3,3-disubstituted 3H-imidazo[l,5-c)imidazole derivatives, which have been isolated when R1 = R2 = Et, Bu, and PhCH,; when R' = R2 = Ph the only product isolated is tentatively assigned the imidazo[l,5-c] imidazole structure. In the reaction with acetylacetone the 1,Zdihydropurine intermediate is unstable and loses acetone to give 2-methyl-6-carbamoylpurine. The aldehydes RCHO [R = Me, Et, (4-MeCH=CH- , c-C,H,O] also react readily with (3) at room temperature to give the corresponding 6-carbamoyl-182-dihydropurine derivatives, which can be isolated when R = Me or Et; these oxidise in solution to afford the corresponding 6-carbamoylpurines.We have reported previously' that the amidinium salt (l), obtained from reaction between N-methylacetonitrilium triffate and diaminomaleonitrile (DAMN), cyclises on treatment 'H NMR spectra were recorded on Hitachi-Perkin-Elmer R24B (60 MHz) or Bruker XL300 (300 MHz) instruments, 13C NMR

A Simple Precursor for Highly Functionalized Fused Imidazo[4,5-b]pyridines and Imidazo[4,5-b]-1,8-naphthyridine

“…Heating diaminomaleonitrile 1 with triethyl orthoformate in dioxane afforded ethyl [2-amino-1,2-dicyanovinyl] imidoformate 2 [21]. Treatment of 2 with appropriate amines, namely 4-methoxybenzylamine and 4-methylbenzylamine catalyzed by aniline hydrochloride, formed (substituted benzyl)-N-(2-amino-1,2-dicyanovinyl)formimidine 3 which underwent intramolecular cyclization in the presence of 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) to form 5-amino-1-(substituted benzyl)-4-cyanoformimidoyl imidazole derivative 4 [27] (Scheme 1 and Section 3).…”

“…In our research group, we are interested in exploring the reactivity of 5-amino-4-(cyanoformimidoyl) imidazoles 4, easily formed by base-catalyzed cyclization of 2-amino-1,2-dicyano formamidines 3 [21].…”

Guanidine: studies on the reaction with ethyl N-(2-amino-1,2-dicyanovinyl)formimidate

“…The regioselective synthesis of purine derivatives 6 has been reported and allowed the preparation of 6-cyano, 11 6-carbamoyl, 6 6-amidino, 12 6-amino 13 and 6-enamino purines. 14 Functionalized imidazo [4,5-b] pyridines 7 were also produced 15 upon reaction with various carbon acids.…”

“…The initial step of the reaction sequence (Scheme 1) is the formation of an amidine 3 from the reaction of imidate 1 and a primary amine 2. Ammonia, 6 alkyl 7 and aryl 8 amines, hydrazines 9 and hydroxylamine ethers 10 have successfully been used in this reaction and the resulting amidine was isolated in two different tautomeric forms (3A and 3B). A combination of different configurations can also be envisaged for the amidine function but this seems to have little influence on the intramolecular cyclization reaction to generate the substituted imidazole 4 or 5 upon addition of base.…”

Revisiting the Reaction Between Diaminomaleonitrile and Aromatic Aldehydes: a Green Chemistry Approach

“…It has been used as a precursor for producing nucleotides and for synthesising a wide variety of heterocyclic compounds [1] including purines [2,3], pyrimidines [4], pyrazines [5] (some which are widely employed in the fluorescent dye industry [6]), imidazoles [7], biphenylenes [8], porphyrazines (which have great potential in optical sensor technology [9]) and diimines that are used as catalysts [10]. The reaction of DAMN with aromatic aldehydes is widely known to produce monoimines [11].…”