Reaction Steps
A mixture containing 7-bromo-9-cyclopropyl-6-fluoro-9H-isothiazolo[5,4-b]quinoline-3,4-dione (7, 100.0 mg, 0.28 mmol), 1-acetyl-4-tributylstannyl-1,2,3,6-tetrahydropyridine (190.0 mg, 0.46 mmol), tetrakis(triphenylphosphine)palladium(0) (16.0 mg, 0.014 mmol), and dimethylformamide (6.0 mL) Is sparged with argon gas and irradiated with microwaves (5×10 min irradiations at 130° C.). (For cross-coupling experiments described previously using C with conventional thermal heating, see: (a) Laborde, E.; Kiely, J. S.; Culbertson, T. P.; Lesheski, L. E. J. Med. Chem. 1993, 36, 1964-1970. (b) Kiely, J. S.; Laborde, E.; Lesheski, L. E.; Bucsh, R. A. J. Heterocyclic Chem. 1991, 28, 1581-1585. (c) Laborde, E.; Kiely, J. S.; Lesheski, L. E.; Schroeder, M. C. J Heterocyclic Chem. 1990, 28, 191-198) The resulting yellow solution is evaporated to dryness under reduced pressure (−6 mm Hg, 60° C.). The recovered solid is dissolved in a mixture containing 10% methanol in methylene chloride (10 mL), precipitated via addition of hexanes (100 mL), and collected by filtration. This process is repeated once. The product is purified further by flash column chromatography (eluting with 10% methanol in methylene chloride, Rf 0.50) to give pure 26 as a yellow solid (98% purity by HPLC). mp 243-244° C. 1H NMR (CDC3/CD3OD (12:1 v/v), 50° C.): δ 1.32 (m, 2H, c-Pr CH2), 1.45 (m, 2H, c-Pr CH2), 2.18 (s, 3H, NC(O)CH3), 2.65 (m, 2H, NCH2CH2), 3.45 (m, 1H, c-Pr CH), 3.73 (m, 1H, NCH2CH2), 3.87 (m, 1H, NCH2CH2), 4.23 (m, 1H, NCH2CH), 4.31 (m, 1H, NCH2CH), 6.19 (m, 1H, NCH2CH), 7.88 (d, JH-F=6.0 Hz, 1H, quinolone H-8), 8.08 (d, JH-F=11.0 Hz, 1H, quinolone H-5). 19F{1H} NMR (CDCl3/CD3OD (12:1 v/v), 50° C.): δ −119.4 (s). NMR spectroscopic data collected at room temperature indicated that two conformational isomers were present. LCMS m/z calcd for C20H18FN3O3S ([M]+) 399. Found 400 ([M+H]+). HRMS m/z calcd for C20H18FN3NaO3S ([M+Na]+) 422.0951. Found 422.0951.
