[Synthesis]
Example 7: Synthesis of (R)-N-(4-{1-[3-(4-tert-butyl-benzyl)-ureido]-ethyl}-2-fluoro-6-vinyl-phenyl)-methanesulfonamide; Step i: Preparation of 1-(4-amino-3-fluorophenyl)ethanone. In a 25 mL two-necked round-bottomed flask, filled with argon protection, a DMF solution of 2-fluoro-4-iodoaniline (1500 mg, 6.33 mmol) was added. Palladium(II) acetate (42.62 mg, 0.19 mmol), 1,3-bis(diphenylphosphino)propane (156.65 mg, 0.38 mmol, 0.06 equiv.), thallium(I) acetate (1834.19 mg, 6.96 mmol), and butyl vinyl ether (1.64 mL, 12.66 mmol, 2 equiv.) were then added sequentially. The reaction mixture was heated and stirred for 15 hours. After the reaction was completed, the mixture was poured into THF and 10% HCl solution was added slowly. The reaction mixture was extracted with ethyl acetate (300 mL x 3) and the organic phases were combined and washed sequentially with water and brine. The organic layer was dried with anhydrous Na2SO4, filtered and purified by column chromatography (n-hexane: ethyl acetate=3:1) to give a light yellow solid product (343.0 mg, yield 35.40%). Melting point: 77-79°C; IR (KBr pressed sheet, cm^-1): 3373, 3326, 1663, 1296; 1H NMR (400 MHz, CDCl3): δ 7.53 (m, 2H), 6.69 (m, 1H), 3.41 (s, 2H), 2.43 (s, 3H). |