반응 #8583

반응 방정식

(S)-(−)-9,10-Difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid

N-methylpiperazine

→

crystals

수율 51.9%

(3S)-(−)-9-Fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid

수율 51.9%

용매

dimethyl sulfoxide

반응 조건

후처리

1. 1
   기타After evaporating the solvent, ethanol (2 ml)
2. 2
   workup.ADDITIONwas added to the residue
3. 3
   기타The solid thus precipitated
4. 4
   여과was collected by filtration
5. 5
   세척washed successively with a small amount of ethanol and ether
6. 6
   세척eluted with a lower layer solution of chloroform-methanol-water (7:3:1) to thereby give (S)-(−)-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid
7. 7
   기타purifying

실험 절차

(S)-(−)-9,10-Difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid (21 mg) and N-methylpiperazine (30 mg) were dissolved in anhydrous dimethyl sulfoxide (3 ml) and stirred at 130 to 140° C. for 1 hour. After evaporating the solvent, ethanol (2 ml) was added to the residue. The solid thus precipitated was collected by filtration and washed successively with a small amount of ethanol and ether. 14 mg of the obtained powder was subjected to silica gel column chromatography with the use of 5 g of silica gel and eluted with a lower layer solution of chloroform-methanol-water (7:3:1) to thereby give (S)-(−)-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid. The above-described filtration mother liquor was fractioned and subjected to thin layer chromatography (silica gel, 20×20 cm, 0.5 mm), thereby purifying by developing with a lower layer solution of chloroform-methanol-water (15:3:1). The products were combined to thereby give 14 mg of crystals of the target compound. Melting point: 220 to 228° C. (decomposition).

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