9-Fluoro-2,3-dihydro-3-methyl-10- -7-pyrido

The solid state structure of (3>S,8 Sj-10-(8-amino-6-azaspiro[3,4]octan-6-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7//-pyrido[l,2,3-dfe]-l,4-benzoxa-zine-6-carboxylic acid (218) was determined by X-ray diffraction study (98CPB1710). The structure of 6,10-dihydropyrido[2,l-c][l,4]benzoxazine-6,10-dione 219 was established by X-ray diffraction analysis. It contains a crystal solvate with /j-xylene (99MI40). 

Treatment of ethyl 10-methylthio-9-fluoro-3-methyl-2,3-dihydro-7-oxo-7//-pyrido[l,2,3- 7e]-l,4-benzoxazine-6-carboxylate with oxone in aqueous MeOH at 0°C afforded 10-methylsulfonyl derivative (99H(51)1563). Methylthio group in a 7-(4-methylthiophenyl)-5-oxo-2,3-dihydro-5//-pyrido[l,2,3- 7e]-l,4-benzoxazine-3-carboxamide was oxidized to a sulfoxide and a sulfone group (OOMIPl). 

Carboxyl group of (-)-9-fluoro-3-methyl-7-oxo-10-[(3S)-3-(tert-butoxy-carbonylamino)pyrrolidino]-2,3-dihydro-7//-pyrido[l,2,3- 7e]-l,4-benzoxa-zine-6-carboxylic acid was converted into l-nitro-2-oxoethyl group in 45% yield by treatment with l,l -carbonyldiimidazole in boiling CFICI3 for 18h, then with MeN02 in the presence of KOr-Bu for another 18 h (96MI12). 6-(2,2-Diethoxycarbonyl)acetyl derivative formed from the aforementioned 6-carboxylic acid, when it was treated with l,l -carbonyldiimidazole in... 

Hydrolysis of ethyl 9-fluoro-10-(4-methylpiperazino)-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylate in a boiling mixture of AcOH and 35% HCl afforded 7 HCl (97USP5703233). That of (3S)-3-methyl-10-(2,6-dimethyl-4-pyridyl)-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- e]-l,4-benzothiazine-6-carboxylate gave the 6-carboxylic acid (OOMIPIO). 7-Oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylic acid was obtained from its ethyl ester by alkalic hydrolysis in 20% yield (99AP19). 

Bromo-3-methyl-7-oxo-2,3-dihydro-77/-pyrido[l, 2, i-de]-1,4-ben-zothiazine-6-carboxylate 333 was prepared in the reaction of l-(2-bromo-l-methylethyl)-7-bromo-8-fluoro-4-oxo-l,4-dihydroquinoline-3-carboxylate 332 and Na2S (OOMIPIO). 

Fluoro-3-methyl-10-(4-methyl-l-piperazinyl)-7-oxo-2,3-dihydro-7/7-pyrido[l,2,3-carboxylic chloride has been used as an ionizable chromophoric reagent for the analysis of primary amines <2005ELP621>. 

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). 

Reaction of diacetatoboron chelate 198 with cyclic amines (09USA2009/0156577), 2-aminomethylaziridine (06CCL1431), followed by hydrolysis provided 10-substituted 3(S)-methyl-9-fluoro-7-oxo-2,3-dihydro-7H-pyrido[l,2,3-de][l,4]oxazine-6-carboxylic acids. 

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). 

Nitration of 6-(benzothiazol-2-yl)-10-(4-methylpiperazin-l-yl)-9-fluoro-3(S)-methyl-2,3-dihydro- 7H-pyrido[l,2,3-cfe][l,4]benzoxazin-7-one with cone. HN03 in cone. H2SO4 gave 6-(6-nitrobenzothiazol-2-yl) derivative (09JMC5649). 

Reaction of potassium 9-fluoro-3-methyl-10-(4-methylpiperazin-l-yl)-2,3-dihydro-7H-pyrido[l,2,3-de][l,4]benzoxazine-6-carboxylate with 2-[3-(2,4-dichlorophenoxy)propyl]-3-[(2-chloroacetyl)amino]quinoxa-lin-4(3H)-one gave ester derivative of 2,3-dihydro-7H-pyrido[l,2,3-de] [l,4]benzoxazine-6-carboxylic acid. 3-Amino-2-(aryloxymethyl)quinox-alin-4(3H)-ones were N-acylated with 9-fluoro-3-methyl-10-(4-methyl-piperazin-l-yl)-2,3-dihydro-7H-pyrido[l,2,3-de][l,4]benzoxazine-6-car-boxylic acid chloride in the presence of K2C03 in boiling benzene for 6 h (07MI71). 

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