the partial hydrolysis ot 2,3,4-trifluoronitrobenzene (i) with koh in dmso gives 2,3-difluoro-6-nitrophenol (ii), which by condensation with chloroacetone (iii) by means of k2co3 - ki in refluxing acetone yields 2-acetonyloxy-3,4-difluoronitrobenzene (iv). the reductive cyclization of (iv) with h2 over raney-ni in ethanol affords 7,8-difluoro-2,3-dihydro-3-methyl-4h-benzoxazine (v), which is condensed with diethyl ethoxymethylenemalonate (vi) by heating at 145 c giving the malonic derivative (vii). the cyclization of (vii) by heating at 145 c with ethyl polyphosphate (ppe) yields ethyl 9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7h-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylate (viii), which is hydrolyzed with hcl in refluxing acetic acid affording the corresponding free acid (ix). finally, this compound is condensed with n-methylpiperazine (x) in dmso at 110 c.
hayakawa, i.; hiramitsu, t.; tanaka, y. (daiichi pharmaceutical co., ltd.); benzoxazine derivs.. ep 0047005; us 4382892 .
serradell, m.n.; blancafort, p.; castaner, j.; dl-8280. drugs fut 1983, 8, 5, 395.