[Synthesis]
Procedure for the synthesis of Example 19-4 (Compound 152): thionyl chloride (10.0 mL, 1.5 eq.) and 3-chloro-2-methylbenzoic acid (15.6 g, 91.4 mmol, commercially available from Aldrich) were refluxed in benzene until no more gas was produced. The reaction mixture was cooled to room temperature and concentrated. The concentrate was diluted with dichloromethane and slowly added to a dichloromethane solution of aluminum trichloride (12.2 g, 1.0 eq.) at 10-20 °C. Subsequently, ethylene gas was continuously passed into the mixture for 4 hours and stirred overnight. Upon completion of the reaction, the reaction was quenched with 4N hydrochloric acid solution, the organic layer was separated, and the aqueous layer was extracted with ether (3 x 250 mL). The organic phases were combined and washed sequentially with water (3 x 150 mL), saturated sodium bicarbonate solution (3 x 150 mL) and brine (150 mL), dried over anhydrous magnesium sulfate and concentrated. Concentrated sulfuric acid was added to the concentrate and the mixture was stirred at 85°C for 1 hour. The reaction mixture was cooled to room temperature, quenched with ice water and extracted with ether (3 x 250 mL). The organic phases were combined, washed sequentially with water (3 x 200 mL), saturated sodium bicarbonate solution (3 x 200 mL) and brine (100 mL), dried over anhydrous magnesium sulfate and concentrated. Purification by column chromatography using 20% ethyl acetate/hexane as eluent gave pure 6-chloro-7-methyl-1-indanone (11.9 g, 72% yield). This product was subsequently used in Method 19 for the synthesis of 4-(5-chloro-4-methyl-indan-2-yl)-1,3-dihydro-imidazole-2-thione (compound 152).1H NMR (300 MHz, methanol-d4) δ 7.16 (d, J = 8.5 Hz, 1H), 7.02 (d, J = 8.5 Hz, 1H), 6.62 (s, 1H), and 3.59-3.52 (m, 1H), 3.31-3.24 (m, 2H), 3.00-2.92 (m, 2H), 2.30 (s, 3H). |