2-bromo-1-(2,4-dimethylphenyl)ethanone

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

Procedure: A mixture of 5-chloropyrimidin-2-one (425 mg) and 2-bromo-2',4'-dimethylacetophenone (682 mg) in triethylamine (1 ml) and ethanol (20 ml) was stirred at ambient temperature for 2 hours. The reaction mixture was diluted with water and the solid filtered off. the solid filtered off

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

Procedure: A solution of 4.76 g (0.021 mol) of 1-bromo-2-(2,4-dimethylphenyl)-2-oxoethane and 1.76 g (0.021 mol) of 1-methylimidazole in 50 ml of diethyl ether was stirred at room temperature for approximately 21 hours. The reaction solvent was decanted and the residue was washed with diethyl ether. The residue was recrystallized from acetonitrile/ethyl acetate to afford 3.32 g of the title product as white crystals. (51% yield) mp=179°-181° C. The reaction solvent was decanted the residue was washed with diethyl ether The residue was recrystallized from acetonitrile/ethyl acetate

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

Procedure: A solution of 4.76 g (0.021 mol) of 1-bromo-2-(2,4-dimethylphenyl)-2-oxoethane and 1.76 g (0.021 mol) of 1-methylimidazole in 50 ml of diethyl ether was stirred at room temperature for approximately 21 hours. The reaction solvent was decanted and the residue was washed with diethyl ether. The residue was recrystallized from acetonitrile/ethyl acetate to afford 3.32 g of the title product as white crystals. (51% yield) mp=179°-181° C. The reaction solvent was decanted the residue was washed with diethyl ether The residue was recrystallized from acetonitrile/ethyl acetate

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

Procedure: Using the procedure described in Example 5, treatment of a solution of L-proline-L-isoleucine benzylamide (60 mg, 0.19 mmol), with triethylamine (130 uL, 0.94 mmol, 5.0 eq), and 2-bromo-2',4'-dimethylacetophenone (52 mg, 0.23 mmol, 1.2 eq) in THF (7 mL), provided a crude product. A portion of the product was purified by preparative TLC to provide 19 mg (21%) of L-isoleucine, N-[1-(2-(2,4-dimethylphenyl)-2-oxoethyl)-L-prolyl] benzylamide. provided a crude product A portion of the product was purified by preparative TLC

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

Procedure: Using the procedure described in Example 5, treatment of a solution of L-proline-L-isoleucine benzylamide (60 mg, 0.19 mmol), with triethylamine (130 uL, 0.94 mmol, 5.0 eq), and 2-bromo-2',4'-dimethylacetophenone (52 mg, 0.23 mmol, 1.2 eq) in THF (7 mL), provided a crude product. A portion of the product was purified by preparative TLC to provide 19 mg (21%) of L-isoleucine, N-[1-(2-(2,4-dimethylphenyl)-2-oxoethyl)-L-prolyl] benzylamide. provided a crude product A portion of the product was purified by preparative TLC

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

Procedure: A solution of 4.76 g (0.021 mol) of 1-bromo-2-(2,4-dimethylphenyl)-2-oxoethane and 1.76 g (0.021 mol) of 1-methylimidazole in 50 ml of diethyl ether was stirred at room temperature for approximately 21 hours. The reaction solvent was decanted and the residue was washed with diethyl ether. The residue was recrystallized from acetonitrile/ethyl acetate to afford 3.32 g of the title product as white crystals. (51% yield) mp=179°-181° C. The reaction solvent was decanted the residue was washed with diethyl ether The residue was recrystallized from acetonitrile/ethyl acetate

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

Procedure: 4-[4-(2,4-Dimethyl-phenyl)-thiazol-2-yl]-2′-nitro-biphenyl-2-carboxylic acid (126 mg, 47%) was prepared from 2′-nitro-4-thiocarbamoyl-biphenyl-2-carboxylic acid methyl ester (which may be prepared as described for Intermediate 4) and 2-bromo-1-(2,4-dimethylphenyl)ethan-1-one (available from ASDI Incorporated) using the procedure described for the preparation of Example 1. 1H NMR (300 MHz, DMSO-d6) δ 8.52 (d, J=1.8 Hz, 1H), 8.10-8.18 (m, 2H), 7.85 (s, 1H), 7.76 (t, J=7.7 Hz, 1H), 7.11-7.40 (m, 4H), 2.48 (s, 3H), 2.34 (s, 3H). described for the preparation of Example 1

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

Procedure: A mixture of 5-chloropyrimidin-2-one (425 mg) and 2-bromo-2',4'-dimethylacetophenone (682 mg) in triethylamine (1 ml) and ethanol (20 ml) was stirred at ambient temperature for 2 hours. The reaction mixture was diluted with water and the solid filtered off. the solid filtered off

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

Procedure: A solution of 4.76 g (0.021 mol) of 1-bromo-2-(2,4-dimethylphenyl)-2-oxoethane and 1.76 g (0.021 mol) of 1-methylimidazole in 50 ml of diethyl ether was stirred at room temperature for approximately 21 hours. The reaction solvent was decanted and the residue was washed with diethyl ether. The residue was recrystallized from acetonitrile/ethyl acetate to afford 3.32 g of the title product as white crystals. (51% yield) mp=179°-181° C. The reaction solvent was decanted the residue was washed with diethyl ether The residue was recrystallized from acetonitrile/ethyl acetate