Unreported 2-substituted 4H-pyrido[e][1,3]oxazin-4-ones are synthesized via an unprecedented intramolecular O-arylation of N-aroyl- and N-heteroaroyl-(iso)nicotinamides under microwave irradiations, in good to excellent yields. The broad applicability was demonstrated by 24 examples with a variety of substituents at the 2-position of the final compounds and 3 possible positions for the nitrogen atom of the pyridine ring. In addition, transformation of one of these compounds into 2-hydroxypyridyl-substituted 1,2,4-triazole and 1,2,4-oxazinone was realized. This approach opens a rapid access to a new bicyclic heteroaromatic chemical series with high potential in medicinal chemistry.

Pyridyl-substituted 1,3,5-triazines were synthesized in good to excellent yields via an unprecedented one-step cyclocondensation of 4H-pyrido[1,3]oxazin-4-ones with amidines at room temperature or under microwave irradiations. The broad applicability was demonstrated by 33 examples with a variety of amidines and three different 4H-pyrido[1,3]oxazin-4-one chemical series. In addition, a one-pot process from 4H-pyrido[1,3]oxazin-4-one precursors (imide sodium salts) was developed and led to the desired triazines compounds, thus allowing a one-step economy in their global synthetic preparation. This approach provides rapid access to pyridyl (or pyridone)-substituted 1,3,5-triazines with high potential in various fields of application.

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A complete study on the preparation of original halogen‐containing 4H‐pyrido[e][1,3]oxazin‐4‐ones and their transformation into 1,2,4‐oxadiazoles and 1,2,4‐triazoles is presented. Starting from pyridyl‐imide sodium salts, the efficiency of the intramolecular O‐arylation was studied on three series of compounds, with different fluoro‐, chloro‐, and bromophenyl substituents at the C‐2 position. The final halogenated compounds are of interest as new synthons for future functionalisation. We also present the discovery of a new, rapid, and complementary access to 2‐substituted 4H‐benzo[e][1,3]oxazinones. Finally, the one‐step transformation of some of these pyrido‐oxazinones into the corresponding hydroxypyridyl‐substituted 1,2,4‐oxadiazoles and 1,2,4‐triazoles was explored, and the regioselectivity of the reaction was proved by X‐ray crystallography.

Access to Pyridyl-Substituted 1,3,5-Triazines from 4H-Pyrido[1,3]oxazin-4-ones via a Cyclocondensation Process. -A broad spectrum of the desired triazine derivatives is available from 4H-pyrido[1,3]oxazin-4-one substrates and amidines (used either as free base or salt) and microwave irradiation is found to be optimal for the procedure. Imide sodium salt precursors such as (XVI) or (XVII) can also be used: In this case, the two-step one-pot approach to the heterocyclic system has a high synthetic potential. -(LE FALHER, L.; BEN AYAD, O.; ZIYARET, O.; MAMONTOV, A.; BOTUHA*, C.; THORIMBERT, S.; SLOWINSKI, F.; J. Org. Chem. 79 (2014) 14, 6579-6589, http://dx.doi.org/10.1021/jo5010668 ; Inst. Parisien Chim. Mol., CNRS, Univ. P. et M. Curie, F-75005 Paris, Fr.; Eng.) -Lehmann 02-169

Preparation of Halogen-Containing 4H-Pyrido[e][1,3]oxazin-4-ones and TheirTransformation into 2-Hydroxypyridinyl-Substituted 1,2,4-Oxadiazoles and 1,2,4-Triazoles. -The preparation of the title compounds starts from brominated pyridines (I), (X), and (XVI) and proceeds via imide sodium salts followed by intramolecular O-arylation. Thus, a broad spectrum of the desired heterocycles is available, substituted in many cases with halogenated aryl substituents for further functionalizations. In the series derived from (I), o-halogenation leads to complex reactions: a low yield is obtained from chlorinated salt (IIIb), whereas no product is formed from the brominated analogue (IIIc). Finally, the fluorinated salt (VIII) produces the unexpected oxazine (IX). Salts of type (XVIII) have to be transformed immediately due to their instability. Simple one-step procedures allow preparation of oxadiazoles [cf. (V)] or triazoles [cf. (VI) and (XV)] from the pyrido-oxazine nucleus. -(LE FALHER, L.; BEN AYAD, O.; ZIYARET, O.; BOTUHA*, C.; THORIMBERT, S.; SLOWINSKI, F.; Eur. J. Org. Chem. 2015, 17, 3830-3840, http://dx.doi.org/10.1002/ejoc.201500277 ; Inst. Parisien Chim. Mol., CNRS, Univ. P. et M. Curie, F-75005 Paris, Fr.; Eng.) -Lehmann 44-194