1.3- Oxazin-6-ones pyridines

In an approach to the AB rings of rubrolone 65, Boger examined the use of oxazinones as a replacement for triazines. Reaction of l,3-oxazin-6-one 66 with enamines 67 produced the corresponding pyridines 70. The reaction proceeds in a manner analogous to the triazines however, instead of losing nitrogen, these systems lose CO2 via the intermediate bicyclo[2.2.2]octanes 68. The resultant 69 then loses pyrrolidine as in the triazine example. 

Substituted perhydropyrido[l,2-c][l,3]oxazines 83 were obtained by the cyclization of l-(/er/-butoxycarbonyl)-2-(2-hydroxyalkyl)piperidines 104 in pyridine on the action of MeS02Cl at room temperature (96CJC2434). Cyclization of c/5-2,6-H- l-(methoxycarbonyl)-2-(2-acetoxyhexyl)-9-methox-ypiperidines 105 and 106 in THF in the presence of KO/-Bu yielded 3-butyl-9-methoxyperhydropyrido[l,2-6 ][l,3]oxazin-l-ones 94. Treatment of l-(/erc-butoxycarbonyl)-2-[2-hydroxy-2,2-di(2-propyl)ethyl]piperidine with NaH in boiling THF yielded 3,3-di(2-propyl)perhydropyrido[l,2-c][l,3] oxazin-l-one (01JA315). 

Treatment of 3-phenylperhydro[l, 3]oxazolo[3,2-a]pyridine-5-carboxylates 303 and 304 with BF3 Et20 in THE, followed by reduction with NaBD4 afforded 6-deutero-4-phenylperhydropyrido[2,1 -c][l, 4]oxazin-1 -ones 220 and 222 (97JA6446). 

Treatment of benzoylisocyanate 1562 with trimethylsilyl ketene 1563 gives the oxazine 1564 which reacts, e.g., with enamines 1565 to give pyridine-2-ones 1567,... 

Dihydro- 1,4-oxazines (268) are available through the treatment of acetals (267) with phosphorus pentoxide in pyridine (79SC631), while 2-ones (270) and 6-ones (272) are formed by the cyclodehydration of N-phenacylglycinates (269) with acid (79CR(C)(288)22l) and the hydrobromides of O-alkylamino acids (271) with base (77CB3615). 

Quinoline and isoquinoline with MP in ether yield benzoindolizines,382 on exact analogy with the pyridine series. Isoquinoline with but-l-yn-3-one in acetonitrile give the isoquinolone 330, doubtless due to the presence of traces of water, but in ether an uncommon reaction giving an oxazine (331) is observed.299 In the presence of proton donors, isoquinoline behaves like pyridine with MP241,382 or but-l-yn-3-one,299 but the anion only reacts at position 1, giving products such as 332. The anion adds at position 4 in a few similar reactions involving quinolines.241,299... 

The treatment of oxazolo[3,2-a]pyridine 449 with Et3SiH in the presence of TiCl4 afforded two different products depending on the reaction temperature (07TA1585). AtO °C 1,3,4,6,7,8-hexahydropyrido[2,l-c][l,4]oxazin-l-one 450 was the product in 35% yield, while below —40 °C piperidine derivative 451 was obtained. 

Another derivative was synthesized starting from 5-aminopyridazine-4-carboxylic acid (156). Its reaction with benzoyl chloride in pyridine gave 2-phenylpyridazino[4,5-[Pg.762]

Pyrido[2,3-b] [l,4]oxazin-2-ones 88 were prepared [55] from 2-chloro-3-hydroxypyridine 84 and 2-chloroacetamide derivatives 85 (Scheme 32). hi principle, the intermediate anion 86 could cyclize through the pyridine C-2 or C-3 carbon atoms (the Smiles rearrangement). The best results were obtained when cesium or rubidium carbonate in boiling MeCN or cesium carbonate in DMF at 90-100 °C were used as the base (Table 4). 

The synthesis of heterocycles via rDA processes includes the preparation of heterocycles with two different heteroatoms. Furo[3,4-c]pyridine (218), a previously unknown polyheterocyclic, has beat achieved by FVP of adduct (217) (equation 98). The heteropentalene Aieno[3,4-6]fuian (220) has been synthesized by a reaction pathway based upon rDA formation of polyheterocycle (219) (equation 99). Other heterocycles prepared via rDA reactions that contain two differoit heteroatoms include 6H-l,3-oxazin-6-one (221) and 3-arylisoxazoles (222). ... 

Certain ylides react with arylcyclopropenones via 1,4-addition to give a-pyrone and its heterocyclic derivatives the formation of the l,3-oxazin-6-one 336 from reaction of the pyridine-iV-imine 335 with 14 is representative. Pyrimidones, pyridines and related... 

Cyclization of 2-(l-alkoxycarbonyl-2-piperidinyl)ethanols with mesyl chloride in pyridine (91X3805) or in the presence of NEts [88CPB1597 90H(30)855], with NaH [83H(20)601 85H(23)831] or with KOH in boiling methanol (91CJC211), led to perhydropyrido[l,2-c][l,3]oxazin-l-ones. 

Pyridine-2-carboxamides may be prepared in a ring-opening reaction of 2-methyl- or 2-phenylpyrido[3,2-d][l,3]oxazin-4-one with various amines.424... 

Ring-opening reactions of 2-phenylpyrido[3,4- /][l,3]oxazin-4-oncs with ammonia, aniline, or 3-nitroaniline afford the corresponding 3-(acylamino)pyridine-4-carboxamides, which may be cyclized thermally to give pyrido[3,4-r/]pyrimidin-4(3/f)-ones, e.g. 4.11 453... 

If the 2-position bears hydrogen or methyl, ring-opening reactions of 4//-pyrido[3,4-r/] [1,3]oxazin-4-ones with ammonia, hydroxylamine, hydrazine, or aniline to give the 3-(acyl-amino)pyridine-4-carboxamides are directly followed by ring closure to yield the corresponding pyrido[3,4-ri]pyrimidin-4(3//)-ones.463,484... 

Spirocyclic pyrido-l,3-oxazin-2-ones (277) can be obtained by the reactions of 2-amino-3-(l-hydroxycycloalkanyl)pyridines (276) with butyllithium and diethyl carbonate (Equation (26)) <89JHC113>, and l,4-dihydro-3,l-benzoxazin-2-ones (279) are available through the reactions of 2-benzoylphenyl isocyanates (278) with alcohols. The former are prepared by Friedel-Crafts acylation of benzene by 2-isocyanatobenzoyl chloride in the presence of aluminum(III) chloride (Scheme 81) and the whole process can be run as a one pot reaction <87JCR(S)96>. 

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