1.3- Oxazine-4,6-diones

Despite that the thiophene ring is considered as a bioisoster of the benzene ring, the synthesis and chemistry of thiophene analogs of heterocycles with therapeutic interest remain poorly studied. One of the most recent examples concerns the synthesis of new substituted thioisatoic anhydrides (6 and 7-arylthieno[3,2-d] [1,3]oxazine-2,4-diones), which were prepared on a large scale under microwave irradiation conditions. A small library of thiophene ureidoacids was easily performed using a Normatron microwave reactor (500 W) with high yields and good purity [4,5] (Scheme 4). 

Alkylated acetoacetanilides 427 were cyclized to 1,3-oxazine-2,4-diones 428 on treatment with ethyl chloroformate in the presence of NaH (Equation 45). The yields of this stepwise O-acylation/cyclization reaction were strongly dependent on the electronic properties of the aromatic substituents the yield was substantially higher for the p-methyoxyphenyl-substituted derivative than for the />-chlorophenyl analog <2006H(68)465>. 

A novel acid-catalysed rearrangement of 2-hydroxy-2-phenylazo-y-butyrolactone (45) to the interesting A-substituted tetrahydro-1,3-oxazine-2,4-dione derivative (46) has been reported.58 The photo- and thermo-chemistry of diazo(2-furyl)methane and diazo(3-furyl)methane have been investigated59 using matrix isolation techniques, and 3,7-diphenylpyrano[4,3-c]pyran-l,5-diones have been prepared60 from 5,5 -diphenyl-... 

Oxazine-2,4-dione is an inhibitor of Escherichia coli and other bacteria. It may be halogenated directly at C-5 by chlorine, bromine, or iodine monochloride <76CCC2059>. Its derivatives undergo deuterium exchange at this site <78TL1693>. 

Benzonitrile, 3,5-diiodo -hydroxy-. Seeloxynil 1H-Benzo[D][1,3] oxazine-2,4-dione. Seelsatoic anhydride... 

Snyder DS, Tradtrantip L, Yao C, Kurth MJ, Verkman AS (2011) Potent, metaboUcaUy stable benzopyrimido-pyrrolo-oxazine-dione (BPO) CFTR inhibitors for polycystic kidney disease. J Med Chem 54 5468-5477... 

Presset M, Coquerel Y, Rodriguez J. Microwave-assisted domino and multicomponent reactions with cyclic acylke-tenes expeditious syntheses of oxazinones and oxazin-diones. Org. Lett. 2009 11 5706-5709. 

ANTIBIOTICS - NUCLEOSIDES AND NUCLEOTIDES] (Vol 3) 5-b-D-Ribofuranosyl-l,3-oxazine-2,4-dione [32388-21-9]... 

Dibenz[h,e]azepine-6,11-diones ent-Morphinan nomenclature, 1, 29 Morphinan, 1,2,3,4-tetrahydro-nomenclature, 1, 29 14-a-Morphinan, N-methyl-synthesis, 1, 480 Morphinans nomenclature, 1, 29 as pharmaceuticals, 1, 148 synthesis, 2, 377 Morphine, 2, 512 as analgesic, 1, 167 as metabolite of normorphine, 1, 235 as pharmaceutical, 1, 146, 147, 148 synthesis, 1, 480 Morphine alkaloids structure, 4, 534 Morphin-7-en nomenclature, 1, 29 Morphinone, dihydro-as pharmaceutical, 1, 147 Morpholine — see also 1,4-Oxazine, tetrahydrocarcinogenicity, 1, 229 corrosion inhibitor, 1, 409 metabolism, 1, 226 nomenclature, 3, 996 structure, 2, 5 synthesis, 2, 89 Morpholine, 4-aciyloyl-polymers, 1, 291 Morpholine, alkenyl-polymers, 1, 291... 

H-l,2-Oxazine-3-carboxylic acid, 5,6-dihydro-synthesis, 1, 484 Oxazine-4,6-dione, 2-methylene-synthesis, 3, 1031... 

Reaction of 8-methylperhydropyrido[l,2-c][l,3]oxazine-l,3-dione 91 with PhCH2NH2 then PhCOCl and 4-methoxyphenol afforded ring-opened products 92 and 93, respectively (00JA11009). 

Reaction of tetrahydropyridin-4-one 119 and l,r-carbonyldiimidazole furnished l,3,4,4n,5,6-hexahydropyrido[l,2-c][l,3]oxazine-l,6-dione 120 (99JA2651). Similarly, pyrido[l,2-c][l,3]oxazine-l-one 121 and [1,3] oxazino[4,3-n]isoquinoline-4-one 122 were prepared from the respective 2-(2-hydroxypropyl)piperidine and l-(2-hydroxypropyl)-1,2,3,4-tetrahy-droisoquinoline (99JOC3790). Reaction of a 2 1 diastereomeric mixture of l-(l,2-dihydroxyethyl)-6,7-dihydroxy-l,2,3,4-dihydroisoquinolines 123 and 124 with l,l -carbonyldiimidazole gave a 2.7 1 mixture of 1,9,10-trihy-droxy-l,6,7,ll/)-tetrahydro-2//,4//-[l,3]oxazino[4,3-n]isoquinoline-4-ones 125 and 126, which were separated on preparative TLC plate (99BMC2525). 

Treatment of perhydropyrido[2,l-c][l,4]oxazine-3,6-dione 232 with B2H6 yielded (—)-(2i )-[(2S)-hydroxymethyl)piperldin-1 -yl]-2-phenylethanol (233) (00T233). Reduction of ( )-(3i ,4i ,9aS)-4-methyl-3-phenylperhydropyr-ido[2,l-c][l,4]oxazin-3-ol (234) with NaBH4 yielded ring-opened product 235 (97JHC1813). 

Depending on the substitution of the 3-hydroxycarbohydroxamic acids, 1,4,2-dioxa-zole-5-ones, l,3-oxazine-2,4-diones, or 3-ethenyl-l,4,2-dioxazole-5-ones are formed with... 

Allylpiperidines were formed from 3-iodomethylperhydropyrido[l,2-f][l,3]oxazin-l-ones by treatment with Zn in AcOH <2002OL3459>. l-Methyl-2-(2-hydroxyalkyl)piperidines were prepared from 3-substituted perhydropyr-ido[l,2-tf][l,3]oxazin-l-ones with lithium aluminium hydride (LAH) in boiling THF and EtzO <2005T1595>. Reaction of 8-methylperhydropyrido[ 1,2-r [ 1.3 ]oxazine-1,3-dione 103 with PhCH2NH2, then PhCOCl and 4-meth-oxyphenol afforded ring-opened products 104 and 105, respectively (Scheme 8) <2000JA11009>. 

Treatment of tert-butyl (2/. )-2-(2-propcny lidene (piperidine-1-carboxylate with McjSil and PhOH yielded 3-substituted-3,4,7,8-tetrahydro-l//,6//-pyrido[l,2-c][l,3]oxazin-l-ones <2005T1595>. Reaction of l-(benzoxycarbonyl)2-styrylpiperidin-4-one with I2 resulted in the formation of r-3,4a-//-/ra r-4-//-4-iodo-3-phenylperhydropyrido[l,2-d-[l,3]oxazine-l,6-dione <2002JOC1972>. A diastereomeric mixture of 3-iodomethylperhydropyrido[ 1,2 z [ 1,3]oxazin-l-ones (e.g., 178) was obtained by intramolecular iodocarbamation of l-(alkoxycarbonyl)-2-allylpiperidines (e.g., 177) with I2 (Equation 34) <1999JOC8402, 2002OL3459>. 

Cyclization of 1-carboxypentyl pipecolinate with bis(2-oxo-3-oxazolidinyl)phosphinic chloride in DMF in the presence of Htinig s base afforded 3-butylperhydropyrido[2,l-f][l,4]oxazine-l,4-dione <1996DEP4440193>. Cyclization of methyl 4-(alr-3,5-H-2-oxomorpholin-5-yl)butyrate in boiling toluene provided ar-4,9a-//-4-phenylper-hydropyrido[2,l-f][l,4]oxazine-3,6-dione <1995H(41)1931, 2000T233>. 

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