6-Aminouracils as precursors for the syntheses of fused di- and tricyclic pyrimidines

Abstract

Bicyclic and tricyclic fused pyrimidine derivatives have received much attention in connection with biologically significant systems such as purines, 1-7 pteridines 8-14 and alloxazines. The synthesis of the above categories has been accomplished by the cyclisation of 6-aminouracil derivatives and ring transformation of other fused pyrimidine-2,4diones. 15,16 In extending our recent work on simple bicyclic xanthines, 6,7 tricyclic alloxazines 17,18 and pyridodi pyrimidines 19 this paper reports a novel synthesis of 3-benzyl-9-methylxanthine (5), 3,9-dimethyl-8-phenylxanthine (7), 7 dipyrimidopyridines 10a-f and pyrimido [4,5-d]pyrimidines 11a-d via Mannich reactions.The synthesis of 3,9-disubstituted xanthines 5,7 has been performed by various approaches [20][21][22] and we report a more favoured sequence from the 1-substituted-6-chlorouracils 1a, b 23,24 (Scheme 1) by reaction with methylamine and N-methyl benzylamine respectively where the 6-amino compounds 2 and 6 were obtained in a good yield. Nitrosation of 2 afforded the 5-nitroso compound 3, which underwent reductive formylation to 4 which readily undergoes intramolecular cyclization with formamide to furnish the xanthine 5 or refluxing the tertiary amine 6 with sodium nitrite in the presence of acetic acid resulted in ring closure in one step giving the 3,9-dimethyl-8-phenylxanthine (7), probably via a 5-nitroso compound 6a and its tautomer 6b. All the products were assigned by 1 H NMR, UV spectra and microanalysis.It was found that the intramolecular cyclisation of 6-(Nalkylanilino)uracils with dimethylformamide (DMF)-POCl 3 25

Synthesis of biologically active and photostable rigid poly(vinyl chloride)

“…The 6-amino-2-thioxo-1H-pyrimidine-4one was prepared by the condensation of thiourea with ethyl cyanoacetate in sodium ethoxide according to the known procedure. 24 The new pyrimidine derivative was prepared by refluxing equimolar ratios of N,N-dimethyl formamide dimethyl acetal DMF/DMA with the previously prepared amino pyrimidine in DMF as solvent for about 10 h. The reaction mixture was poured on ice water that acidified with HCl droplets and then the precipitate was formed. The new dimethyl pyrimidine derivative was collected, crystallized from DMF, and then the melting point was measured using an electrothermal apparatus.…”

Recent Developments in the MCRs Synthesis of Pyridopyrimidines and Spiro‐Pyridopyrimidines

“…Pyrido [2,3-d]pyrimidine derivatives possess wide range of physiological properties, which include antiviral [1], antibacterial [2], diuretic, analgesic [3], anticonvulsive [4,5], anti-inflammatory [6], antipyretic [7], cardiotonic [8,9], antitumoral [10], antihistaminic [11], bactericidal [12], bronchiodilator [13], and also act as a cyclin-dependent kinase 4 inhibitor [14]. Pyrido [3,2-d]pyrimidines act as dihydrofolate reductase inhibitors and tyrosine kinase inhibitors [15].…”

“…To optimize the reaction conditions, different catalysts (Fe +3 -mont., KSF, AcOH, ZnCl 2 , p-TSA, [TEBSA]HSO 4 , and [MBSI]HSO 4 ) and solvent (H 2 O, EtOH, CH 2 Cl 2 , and solvent-free) were screened to prepare a model product. The result showed reaction with [DMBSI]HSO4 as catalyst under solvent-free conditions is the most effective among selected solvents and catalysts. In order to extend the scope of this protocol for the synthesis of other derivatives of pyridopyrimidines, they have investigated the reaction of 6-amino-2-(methylthio) pyrimidin-4(3H)-one, heteroaromatic aldehydes, and Meldrum's acid in the presence of [DMBSI] HSO 4 and obtained pyrido[2,3-d]pyrimidines 55 in high yields (80-90%) and short reaction times (4-6 min) (Scheme 30).…”

One-pot Synthesis of Fused 2-Thiouracils: Pyrimidopyrimidines, Pyridopyrimidines and Imidazolopyrimidines

“…The Mannich reaction of 3(5)-arylaminopyrazoles with primary amines has been described [3] as a route to pyrazolo [3,4-d] pyrimidines. 6-Amino-1-methyl-or 1-(2-chlorobenzyl)-or 1,3-dimethyl-uracil were the key intermediates for the synthesis of pyrimido [4,5-d]pyrimidines via a Mannich base [4,5]. A literature survey revealed no previous reports on 2-thiopyrimido [4,5-d]pyrimidines.…”