Example NINETEEN-5 (compound 153) was synthesized as follows: thionyl chloride (5.73 mL, 79 mmol) was mixed with 2,3-dichlorobenzoic acid (10.0 g, 52.4 mmol, available from Aldrich) in benzene and heated to reflux until no gas was released. After the reaction was completed, it was cooled to room temperature and the reaction mixture was concentrated. The concentrate was diluted with dichloromethane and slowly added to a dichloromethane solution containing AlCl3 (7.0 g, about 53 mmol) at 10-20 °C. Subsequently, ethylene gas was passed into the mixture for 4 h and stirring was continued overnight. At the end of the reaction, the reaction was quenched with 4N HCl and the organic and aqueous layers were separated. The aqueous layer was extracted with ether (3 x 250 mL), the organic extracts were combined, washed sequentially with water (3 x 150 mL), saturated NaHCO3 solution (3 x 150 mL), and brine (1 x 150 mL), and concentrated by drying with MgSO4. The concentrate was mixed with AlCl3 (9.0 g) and NaCl (2.4 g) to form a slurry at 130 °C, followed by stirring at 180 °C for 2 hours. Upon completion of the reaction, it was cooled to room temperature, quenched with ice, and concentrated HCl was added. the mixture was extracted with dichloromethane (3 x 500 mL), the organic layers were combined and concentrated, purified by column chromatography using 20% ethyl acetate/hexanes as eluent to afford 6.8 g (80% yield) of 6,7-dichloro-2,3-dihydro-1H-inden-1-one. The method was further used for the synthesis of 4-(4,5-dichloroindan-2-yl)-1,3-dihydroimidazole-2-thione (compound 153).1H NMR (300 MHz, MeOH-d4) δ 7.31 (d, J = 7.8 Hz, 1H), 7.14 (d, J = 8.1 Hz, 1H), 6.62 (s, 1H), 3.67-3.56 ( m, 1H), 3.42-3.31 (m, 2H), 3.09-2.99 (m, 2H).
