Reaction Steps
A mixture containing 7-bromo-9-cyclopropyl-6-fluoro-9H-isothiazolo[5,4-b]quinoline-3,4-dione (8) (31.8 mg, 0.090 mmol), 30 (68.0 mg, 0.182 mmol), tetrakis(triphenylphosphine)palladium(0) (7.2 mg, 0.006 mmol), dimethylformamide (1.5 mL), and a 1 M aqueous solution of sodium bicarbonate (360 μL, 0.360 mmol) is sparged with argon gas and irradiated with microwaves (5-min irradiation at 120° C.). The resulting green, gelatinous mixture was filtered and evaporated to dryness under reduced pressure (˜6 mm Hg, 40° C.). The recovered residue (orange oil) is washed with diethyl ether (10 mL) to give a yellow solid. This material is dissolved in a mixture containing 25% methanol in chloroform (2.0 mL), precipitated via addition of diethyl ether (10 mL), and collected by filtration; this process is repeated once. The product is washed further with water (2×10 mL) and dried in vacuo to give (rac)-tert-Butyl[6-(9-cyclopropyl-6-fluoro-3,4-dioxo-2,3,4,9-tetrahydro-isothiazolo[5,4-b]quinolin-7-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate as a yellow solid (93% purity by HPLC; the remaining material is 9-cyclopropyl-6-fluoro-9H-isothiazolo[5,4-b]quinoline-3,4-dione). 1HNMR (CDCl3/CD3OD (12:1 v/v), 50° C.): δ 1.10 (m, 2H, c-Pr CH2), 1.21 (m, 2H, c-Pr CH2), 1.48 (s, 9H, C(CH3)3), 1.76 (m, 1H, H-3), 2.10 (m, 1H, H-3), 2.68 (m, 1H, H-1), 2.86 (m, 2H, H-4), 3.08 (m, 1H, c-Pr CH), 3.12 (m, 1H, H-1), 3.94 (m, 1H, H-2), 7.11 (m, 1H, aromatic), 7.20 (m, 2H, aromatic), 7.71 (m, 1H, aromatic), 7.92 (m, 1H, aromatic). 19F{1H} NMR (CDCl3/CD3OD (12:1 v/v), 50° C.): δ −123.8 (s). NMR spectra collected at room temperature contained broad, unresolved signals. LCMS m/z calcd for C28H28FN3O4S ([M]+) 521. Found 522 ([M+H]+).
