2.3- Dihydro-5H-pyrido

Oxidation of 3-hydroxymethyl-2,3-dihydro-5H-pyrido[l,2,3-cfe][1,4] benzoxazin-5-ones with o-iodoxybenzoic acid in DMSO and with Dess-Martin periodinate in CH2CI2 afforded 3-formyl derivatives (08WOP2008/ 120003). Dehydrogenation of ethyl 10-[2-(ferf-butoxycarbonyl)-l,2,3,4,6,8a-hexahydropyrrolo[l,2-a]pyrazin-7-yl]-9-fluoro-3(S)-methyl-7-oxo-2,3-dihydro-7H-pyrido[l,2,3-de][l,4]oxazine-6-carboxylates in the presence of Pd/C with air in MeOH afforded 10-[2-(ferf-butoxycarbonyl)-l, 2,3,4-tetrahydropyrrolo[l,2-a]pyrazin-7-yl] derivatives, which then were deprotected (09BML4933). 

Oxo-2,3-dihydro-5H-pyrido[l,2,3-de][l,4]benzoxazine-3-carbalde-hydes were reacted with tert-bu tyl piperidin-4-ylcarbamate, then the reaction mixture was treated with sodium triacetoxyborohydride to give 3-[4-(ferf-butoxycarbonylamino)piperidin-l-yl)methyl derivatives (08WOP2008/120003). 8-Fluoro-3-oxo-2,3,6,7-tetrahydro-5H-pyrido [l,2,3-cfe][l,4]benzoxazin-7-carbaldehyde was similarly reacted with cyclic amines, then with (polystyrylmethyl)trimethylammonium cya-noborohydride in acidified MeOH (08WOP2008/116815). 

Cyclization of dimesylates 285 in toluene at reflux overnight gave 2,3-dihydro-5H-pyrido[l, 2,3-de] [1,4]benzoxazin-5-ones 286 (09WOP2009/ 104147). 

E)-(Hex-l-enyl)-2,3-dihydro-5H-pyrido[l,2,3-cfe][l,4]oxazine-3-one 362 was obtained in the reaction of BrCH2COBr and quinoline 361, prepared from 8-trimethylsilyloxyquinoline with di-i-butyl hex-1-enylalumi-num (08T197). 

Antibacterial activity in serum of the 3,5-diamino translation inhibitor, compound 511 was determined against Escherichia coli and Pseudomonas aeruginosa (08BML3369). Antileishmanial and cytotoxicity toward macrophages of 2,3-dihydro-5H-pyrido[l,2,3-de][l,4]benzoxazin-5-one was measured (09EJM845). 

Reaction of 9-fluoro-7-oxo-2,3-dihydro7H-pyrido[l,2,3-de][l,4]oxa-zine-6-carboxylate and ferf-butyl (2-mercaptoethyl)carbamate in DMSO at 100 °C for 5 h gave 9-[2-(ferc-butoxycarbonylamino)ethylthio] derivative (06WOP2006/050943). The iodo atom of 9-iodo-7-oxo-2,3-dihydro-7H-pyrido[l,2,3-de][l,4]oxazine-6-carboxylic acids was coupled with 4 -0-(2-allyloxyethyl)azithromicin in MeCONMe2 in the presence of Bu3N and fra s-di-g-acetato-bis[2-(di-o-tolylphosphino)benzyl]dipalladium(II) and di(ferf-butyl)-4-methylphenol at 110-115 °C for 15-17 h to give a mixture of 9-(3-substituted prop-1- and -2-enyl) derivatives (07WOP2007/ 054296). 10-methoxy and 10-cyano-3-hydroxymethyl-2,3-dihydro-5H-pyr-ido[l,2,3-de][l,4]benzoxazin-5-ones were obtained from 10-bromo derivative by reaction with NaOMe in the presence of Cu(I)I at 140 °C in DMF,... 

H,4H-Oxazolo[5,4,3-y]pyrido[3,2-g]quinolin-4-one, 8-hydroxymethyl-6-methyl — see Nybomyein 5H-Oxazolo[2,3-[Pg.731]

Benzo[g indol 2,3-Dioxo-6-mtro-2,3-dihydro- VII/4, 16 5H-[Pg.956]

Thus, novel 2-substituted methyl 2,3-dihydro-1 -methyl-3-oxo-5H-pyrido[4,3-fe] indole-4-carboxylates are available. Since the methyl group at the 1 position is expected to react with various reagents, many 1-substituted derivatives could be produced. 

Stereostructures of perhydropyrido[l,2-c][l,3]oxazines 51 and 52 (06JOC8481, 06TL7923) and (+)-(3R,7R)-7-amino-3-(4-methoxyphenyl)-6,7-dihydro-3H,5H-pyrido[3,2,l-z/]quinazoline-l(2H)-one (06USA2006/ 0004028), the relative configuration of l,llfc-dihydro-2H,4H-pyrimido [6,1 -a] isoqu i nol i n-4-one 53 were determined by X-ray crystallographic analysis (09OL1559). 

N-(3-chloro-5-methoxycarbonylphenyl)-5-bromo-l,2,3,4-tetrahydro-quinoline-8-carboxamide was obtained from 8-bromo-6,7-dihydro-lH,3H,5H-pyrido[3,2,l-z/][3,l]benzoxazine-l,3-dione with methyl 3-amino-5-chlorobenzoate in NMP at 170 °C for 16 h (07WOP2007/028789). 

The treatment of a ferf-butoxycarbonylamino group present in a side chain of 6,7-dihydro-3H,5H-pyrido[l,2,3-cfe]quinoxalin-3-one with 4N HC1 in a dioxane liberated amino group, which was reductively alkylated using heteroaromatic aldehydes followed by the treatment of the formed Schiff bases with NaB(OAc)3H (08WOP2008/003690). 

However, when 36 was heated with a-amino heterocycles or with cyclic 1,3-dicarbonyl or potential 1,3-dicarbonyl compounds, 3-heteroarylp)rr-azol derivatives were obtained. In this manner 36 afforded, when heated with 2-aminopyridine and 3-amino-lH-pyrazol in acetic acid under reflux for 2 h and 5 h, respectively, 3-(5-ethoxy-l-phenyl-lH-pyrazol-3-yl)-4H-pyrido[l,2-fl]pyrimid-4-one (38) and 6-(5-ethoxy-l-phenyl-lH-p5rrazol-3-yl)pyrazolo[l,5-fl]pyrimid-7(lH)-one (39) in 70% and 77% 5deld, respectively. Similarly, 36 afforded with cyclicjS-dicarbonyl compounds, such as 4-hydroxy-6-methyl-2H-pyran-2-one and 5,5-dimethylcyclohexane-l,3-dione by heating in acetic acid for 4 h and 8 h, respectively, the corresponding 3-(5-ethoxy-l-phenyl-lH-pyrazol-3-yl)-7-methyl-2H,5H-pyrano[4,3- 7]pyran-2,5-dione (40) and 3-(5-ethoxy-l-phenyl-IH-pyrazol-3-yl)-7,7-dimethyl-7,8-dihydro-2H-chromene-2,5-dione (41) in 26% and 82% yield, respectively (Scheme 15). 

Upon thermolysis, 3-aroyl-l,2-dihydro-4ff-pyrrolo[2,l-f][l,4]benzox-azine-l,2,4-triones 156a-f in inert aprotic solvents at 168—190 °C led to generation of 4-aroyl-3-aroyloxy-2-(2-oxo-2H-l,4-benzoxazin-3-yl)-lH,5H-pyrido-[2,l-c][l,4]-benzoxazine-l,5-diones 318a—f (Scheme 100)... 

Double ring closure. A soln. of methyl N-acetylglycyl-DL-tryptophanate and polyphosphate ester in chloroform refluxed 4 hrs. 6,ll-dihydro-3-methyl-5-methoxycarbonyl-5H-imidazo[l, 5 l,2]pyrido[3,4-b]indole. Y 71%. F. e. s. Y. Kanaoka, E. Sato, and O. Yonemitsu, Tetrahedron 24, 2591 (1968). 

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