CO[C:3]([C:5]1[CH:6]=[C:7]([F:17])[C:8]([F:16])=[C:9]2[O:14][CH2:13][CH:12]([CH3:15])[NH:11][C:10]=12)=[O:4].ClS([N:22]=[C:23]=[O:24])(=O)=O.C(N(CC)CC)C>ClCCl>[F:17][C:7]1[CH:6]=[C:5]2[C:10]3[N:11]([CH:12]([CH3:15])[CH2:13][O:14][C:9]=3[C:8]=1[F:16])[C:23](=[O:24])[NH:22][C:3]2=[O:4]A solution of 1.5 g (6.2 mmol) of 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine-5-carboxylic acid methyl ester (Example 32a) in 25 mL of dichloromethane is cooled to −20° C. and treated dropwise with 0.92 g (6.5 mmol) of chlorosulfonyl isocyanate. The reaction is stirred at room temperature for 18 hours and the solvent removed in vacuo. The residue is treated with a saturated sodium bicarbonate solution and extracted with dichloromethane. The organic layer is dried (MgSO4), filtered, and concentrated in vacuo. The residue is dissolved in 50 mL of tetrahydrofuran, and the resulting solution is treated with 5.0 g (5.0 mmol) of triethylamine. After heating at reflux for 4 hours, the solvent is removed in vacuo, and the residue is triturated with 5 mL of dichloromethane/ethyl acetate (80:20). The insoluble material is removed by filtration, washed with the above solvent mixture (2 mL) to give 0.25 g of the title compound, mp 259–261° C. The filtrate is chromatographed over flash grade silica gel (230–400 mesh) eluting with dichloromethane/ethyl acetate (80:20) to give 0.38 g of starting material. Continued elution afforded an additional 0.2 g of the title compound. 1H NMR (400 MHz, CDCl3): 11.78 (s, 1H), 7.50 (m, 1H), 4.68 (m, 1H), 4.52 (d, 1H), 4.17 (d, 1H), 1.23 (d, 3H).
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