Reaction Steps
4-chlorobenzene sulfonamide (3.5 g, 18.3 mmol) was added slowly to a suspension of sodium hydride (1.6 g, 55% suspension in mineral oil, 36.6 mmol) in anhydrous DMF (50 mL) under an atmosphere of nitrogen. The mixture was warmed to 40° C. for 1 hour and 2,4-difluoronitrobenzene (2 mL) was added dropwise. This mixture was stirred at 60° C. overnight. The cooled reaction mixture was poured into hydrochloric acid (1 N, 250 mL) and extracted with ethyl acetate (2×50 mL). The organic extracts were washed with water, dried over MgSO4 and evaporated to give a yellow solid. The product was re-crystallized from ethanol. Yield 2.4 g (40%). 1H NMR (400 MHz, CDCl3) δ 6.85 (m, 1H), 7.48 (AB, J=8.3 Hz, 2H), 7.56 (dd, J=10.01, 2.68 Hz, 1H), 7.84 (AB, J=8.3 Hz, 2H), 8.21 (dd, J=9.28, 5.61 Hz, 1H), 10 (bs, 1H). Calculated N 8.47%, C 43.58%, S 9.70%, H 2.44%; Found N 8.54%, C43.89%, S10.10%, H 2.76%. 4-Chloro-N-[5-fluoro-2-nitrophenyl]benzenesulfonamide (1 g, 3 mmol) and N-methylhomopiperazine (0.4 mL) were heated together at 130° C. for 3 hours. The product was allowed to cool, dissolved in CH2Cl2 (50 mL) and washed with aqueous sodium bicarbonate. The organic phase was dried over MgSO4 and evaporated to give 1.05 g of a yellow solid which was re-crystallized from toluene. Yield 0.65 g (51%). 1H NMR (400 MHz, CDCl3) δ 1.98 (q, J=5.62 Hz, 1H), 2.37 (s, 3H), 2.52 (t, J=5.62 Hz, 2H), 2.67 (t, J=5.12 Hz, 2H), 3.55 (t, J=6.35 Hz, 2H), 3.60 (t, J=5.12 Hz, 2H), 6.34 (dd, J=9.77, 2.68 Hz, 1H), 6.86 (d, J=2.68 Hz, 1H), 7.43 (ab, J=8.79 Hz, 2H), 7.79 (ab, J=8.79 Hz, 2H), 8.01 (d, J=9.77 Hz, 1H), 11.6 (br s, 1H). Calculated N 13.19%, C 50.88%, H 4.98%; Found N 13.27%, C 50.99%, H 4.83%.
