2-bromo-N-(4-bromophenyl)acetamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: DMF (20 ml) was added to 1-(4-hydroxyphenyl)ethanone (1.81 g, 13.3 mmol), 2-bromo-N-(4-bromophenyl)acetamide (3.00 g, 10.2 mmol), and potassium carbonate (4.25 g, 30.7 mmol), and the mixture was stirred at room temperature for 16 hrs. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by alumina column chromatography (developing solvent; ethyl acetate), and powderized with ethyl acetate-diisopropyl ether (1:5) to give a phenoxyacetamide derivative (3.44 g). The title compound was obtained by similar operations as in Reference Example 20, Reference Example 21, Example 10 and Example 6 and using this compound. washed with saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the obtained residue was purified by alumina column chromatography (developing solvent; ethyl acetate)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-hydroxy-3-methoxybenzaldehyde (2.02 g, 13.3 mmol), 2-bromo-N-(4-bromophenyl)acetamide (3.00 g, 10.2 mmol) and potassium carbonate (2.12 g, 15.4 mmol) was added propionitrile (10 ml), and the mixture was stirred at 80° C. for one day. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by alumina column chromatography (developing solvent; ethyl acetate), and powderized with ethyl acetate-diisopropyl ether (1:5) to give a phenoxyacetamide derivative (2.93 g). The title compound was obtained by similar operations as in Reference Example 43 and Example 6 and using this compound. washed with saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the obtained residue was purified by alumina column chromatography (developing solvent; ethyl acetate)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Bromo-N-(4-bromophenyl)-acetamide (3.083 g, 10.522 mmol), prepared according to J. Med. Chem., 1996, 4(2), 197-203, benzimidazole (1.24 g, 10.52 mmol) and K2CO3 were combined and dissolved in DMF (60 mL) under nitrogen. The reaction mixture was stirred at room temperature overnight before filtering and purifing by SCX cartridge. The crude product thus obtained was washed with EtOAc to remove excess benzimidazole, yielding the pure product (2.20 g, 63% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 5.17 (2H, s), 7.19-7.28 (2H, m), 7.51 (2H, d, J=12 Hz), 7.51-7.56 (1H, m), 7.57 (2H, d, J=12 Hz), 7.66 (1H, d, J=8 Hz), 8.22 (1H, s), 10.57 (1H, s). MS (ES) m/z: 332.5 [M+H]. before filtering The crude product thus obtained was washed with EtOAc to remove excess benzimidazole