One-Pot Synthesis of 3,4-Dihydro-2H-pyrido[1,2-a][1,3,5]triazin-2-one Derivatives fromN-(2′-Pyridinyl)benzoylacetamide and Nitrosobenzenes

Abstract

S y n t h e s i s o f 3 , 4 -D i h y d r o -2 H -p y r i d o [ 1 , 2 -a ] [ 1 , 3 , 5 ] t r i a z i n -2 -o n e sAbstract: A convenient method leading to fused pyrido[1,2-a] [1,3,5]triazine-2-ones is described. It consists in a one-pot, two-step reaction of N-(2¢-pyridinyl)benzoylacetamide with nitrosobenzenes. On the other hand, N-(2¢-pyridinyl)acetoacetamide provides a C-2 condensation/addition product with nitrosobenzene. N-(2¢-Pyridinyl)benzoylthioacetamide and N-(2¢-pyridinyl)acetothioacetamide with nitrosobenzene undergo oxidative heterocyclisation leading to [1,2,4]thiadiazolo[2,3-a]pyridine derivatives.The interest in the pyrido[1,2-a][1,3,5]triazine system arises from its wide biological activity, 1,2 which comes from its antagonistic effect upon 5-HT 2 and 5-HT 2a serotonin receptors. Such influence can result in: mediating coronary blood flow, 1a decreasing mean arterial blood pressure, 1b and the anti-thrombotic effect 1c in mammals. Other disorders, for whose prophylactic or therapeutic treatment pyrido[1,2-a][1,3,5]triazine derivatives can be used, are those involving airway constriction in human or animals: asthma, emphysema, chronic bronchitis, chronic obstructive pulmonary disease, 2 and various psychotic conditions including schizophrenia, depression, anorectic or bulimic eating disorders, and anxiety in humans. 2c Since 1952, when a possible approach to this system was mentioned for the first time, 3a several general methods of synthesis of pyrido[1,2-a][1,3,5]triazines have been invented, mostly leading to their oxo derivatives.Cyclodimerisation of iso(thio)cyanates leads to pyrido[1,2-a][1,3,5]triazine-2,4-di(thi)ones. 3b-d The other methods include: reaction of isocyanates 4a or active esters of imidodicarbonic 4b or carbonic 4c acid with 2-aminopyridine or other amidines and cyclisation of (thio)urea derivatives 3a or their reaction with isothiocyanate. 4d Pyrido[1,2-a][1,3,5]triazine-4-ones can be obtained from urea derivatives, 5a,b e.g. by their cyclisation, 5a or reaction of aryl isocyanates and unsymmetrical carbodiimides containing 2¢-pyridine ring. 5c,d There are only a few examples of the syntheses of pyrido[1,2-a][1,3,5]triazine-2-(thi)ones known. 3d,6

The applications of β‐keto amides for heterocycle synthesis

“…Zaleska et al reported the synthesis of fused pyrido[1,2‐ a ][1,3,5]triazin‐2‐one derivatives 450 by the reaction of 433 and two equivalent of nitrosoarenes 449 [195]. The reaction may be initialized from the C2‐addition/condensation between β ‐keto amides and the nitrosoarenes.…”

“…The β-keto amide intermediate 447 was prepared by heating equimolar amounts of anthranilic acid 445 with 2,2,6-trimethyl-4H-l,3-dioxin-4-one 446 in xylene while distilling off acetone (Scheme 111) [194]. 3,5]triazin-2-one derivatives 450 by the reaction of 433 and two equivalent of nitrosoarenes 449 [195]. The reaction may be initialized from the C2-addition/condensation between β-keto amides and the nitrosoarenes.…”

New α-Amido-α-aminonitrones As Building Blocks for Constructing ­Heterocyclic Systems

“…In the reactions of ethyl acetoacetate and variously substituted 2-aminopyridines, we obtained the corresponding pyridilides 4a-d (4d had not previously been reported), which were then treated with nitrosobenzene in methanol in an attempt to obtain C-2 disubstituted products of type 3. 6 Using two equivalents of nitrosobenzene yielded unexpected products; the spectra and elemental analyses encouraged the conclusion that the actual products were nitrones 5a-e (Scheme 1).…”

“…It should be noted that the introduction of a phenyl group in place of the methyl group at C3 of 4a totally changes the reactivity of the corresponding pyridylide against nitrosobenzenes. 6 The presence of several nucleophilic centres in a-amidoa-aminonitrones 5 allowed their use in dialkylation reactions with alkyl dihalides. First we examined the reaction with diiodomethane in anhydrous DMF.…”

Development of tuneable green-to-red emitting transparent film based on Nafion with TbIII/EuIII β-diketonate complexes modulated by pH and proton flow

“…HPBA was prepared with 2-aminopyridine and ethyl benzoylacetate in xylene according to a previously reported procedure. 17 1 and 2 were synthesised and crystallised via slow diffusion of Ln(NO 3 ) 3 Á6H 2 O, HPBA and NaOH in MeOH. X-ray crystallographic analysis revealed unexpected dinuclear structures bridged by two PBA À ligands, which are quite different molecular structures reported in ref.…”