Pyrimidines from 1,3,5-triazines

Cyclic, electron-deficient diaza-1,3-butadienes, e. g. pyrimidines, pyridazines, triazines and tetrazines have proved to be an extremely versatile synthetical tool. Extensive studies aimed at the use of these dienes in the synthesis of natural products stem from Boger s group [11]. 

Cyclolinear polymers with cyclotriphosphazene, pyrimidine and triazine units have been applied to enhance the durability of fabrics. The use of polyphos-phazene membranes for the separation of dyes from waste streams has been patented. ... 

One synthesis of isoxazolo[5,4-Z>]pyrimidines from 4-unsubtituted 5-AI has been reported (Section III.C.2). As discussed above for isoxazolo[3,4-Z>]pyridines, the reaction of 3-amino-5-methylisoxazole with carbamate 44 does not produce isoxazolo [3,4-7>]pyrimidines, isoxazolo[2,3-a] 1.3.5-triazines 45 being formed as the only products. Meanwhile, the condensation of 5-amino-3-methylisoxazole with the same carbamate yielded isoxazolo[5,4-Z>]pyrimidine 46 (04KGS496) (Scheme 20). 

Lack of space precludes a fuller presentation of the many papers reporting on the reactivity of relevant heterocyclic thiones derived from imidazole, - - i pyrimidine, - and -triazine. ... 

Baker has developed an approach to selective cytotoxicity based on active-site-directed irreversible inhibitors that combine reversibly with the target enzyme and then inactivate it by exo-alkylation. Using this approach, he has prepared compounds that in vitro selectively inactivate folate reductase from leukemia L1210, but not the enzyme from mouse liver, spleen, and intestine. to vivo, however, the only compound that was effective in prolonging the life of mice with L1210 leukemia did not show selectivity for the reductase from leukemic cells. Hansch has applied regression analysis to a series of pyrimidine and triazine inhibitors of folate reductase. ... 

Pyrimidin-5-amine, 4-methylamino-synthesis, 3, 121 Pyrimidin-5-amine, 4-oxo-purfne synthesis from, 5, 582 Pyrimidinamines acylation, 3, 85 alkylation, 3, 86 basic pXa, 3, 60-61 diazotization, 3, 85 Dimroth rearrangement, 3, 86 electrophilic reactions, 3, 68 Frankland-Kolbe synthesis, 3, 116 hydrolysis, 3, 84 IR spectra, 3, 64 N NMR, 3, 64 nitration, 3, 69 Principal Synthesis, 3, 129 reactivity, 3, 84-88 structure, 3, 67 synthesis, 3, 129 Pyrimidin-2-amines alkylation, 3, 61, 86 basic pK , 3, 60 diazotization, 3, 85 hydrogenation, 3, 75 hydrolysis, 3, 84 mass spectra, 3, 66 Pyrimidin-4-amines acidity, S, 310 alkylation, 3, 61, 86 basic pXa, 3, 61 Schifi base, 3, 85 synthesis, 3, 110, 114 1,3,5-triazines from, 3, 518 Pyrimidin-5-amines basic pXj, 3, 61 hydrogenation, 3, 75 reactions... 

The formal derivation of the analogs, described in the foregoing, represents, from the point of view of systematic organic chemistry, a shift to the derivatives of other heterocyclic systems. In the case of pyrimidine aza analogs we arc dealing with derivatives of symmetrical or asymmetrical triazine in the case of purine aza analogs, the derivatives produced are those of imidazo[4,5]-i -triazine and z -triazolo [4,5-d] pyrimidine. 

The chemistry of the 6-aza analogs of pyrimidine bases which has been developed from the biochemical aspect since about 1956 was based on work reported in relatively numerous older papers. In spite of the fact that 6-azauracil was prepared only in 1947 and suitable syntheses were described only quite recently, substances of this type and methods of their preparation had been known for a long time. The chemistry of 6-aza analogs of pyrimidine bases is therefore relatively closely linked with the chemistry of the 1,2,4-triazine derivatives. 

The cycloaddition reaction of 1,2,4-tiiazines 7V-oxides proceeds differently from the reaction of the corresponding 1,2,4-tiiazines. Thus the 1,2,4-triazine 4-oxide 55 acts only as a diene in the reaction with 1 -diethylaminopropyne to afford 2-methyl-4-(dimethylamino)pyrimidines 111. At the same time the 1,2,4-triazine 4-oxides 55 react with l-(dimethylamino)-l-ethoxyethylene by 1,3-dipolar cycloaddition to give 5-methyl-1,2,4-tiiazines 112 (78CB240). 

Dioxane solutions of 4(5)-aminoimidazole (64) have been treated with several reagents [92JCS(P1)2789], Imidazo[l,5-a]-l,3,5-triazines (65 R = Ph, Me SMe) were obtained by reaction with methyl N-cyanobenzimidate (57 R = Ph), ethyl N-cyanoacetimidate (58 R = Me), and dimethyl yV-cyanodithioiminocarbonate (59 R = SMe). The uncy-clized product (68 R = H) (73%), obtained by condensation with ethyl N-cyanoformimidate (58 R = H), underwent facile cyclization to give the imidazo[l,5-a]-l,3,5-triazine (65 R = H). Likewise, the condensation adduct (69 R = H) (78%) was obtained using ethoxy methyleneurethane (60 R = H) and this underwent base-catalyzed cyclization to give the imidazo[ 1,5-a]-1,3,5-triazinone (67). Imidazo[l, 5-a]pyrimidines (66 R = H, Me) were obtained from the condensation of 4(5)-aminoimidazole... 

Condensation under the usual conditions gave in fact the pyrimidine (XCVI, R = P-CIC6H4) in only 10—15% yield. Even an excess of ethyl acetoacetate raised the yield only inconsiderably (to 30%), the rest of the product being a brown viscous oil, from which the supposed triazine (XCVII) (arising by N2,N -addition) was isolated. The alternative possible N N 5-addition would result in the theoretically possible structure (XCVIII). However, as Paludrine is known to react with ethyl formate at N2,N (372), it is assumed by analogy that ethyl acetoacetate reacts similarly. 

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