935687-49-3

3167-49-5

100-39-0

935687-49-3

Example 46 Procedure for the synthesis of benzyl 6-{3-[7-fluoro-2-(4-fluorobenzyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-propionylamino}- nicotinate: A. Synthesis of benzyl 6-aminonicotinate: to a mixture of DMF (4 mL) containing 6-aminonicotinic acid (1.0 g, 7.2 mmol) and potassium carbonate (1.5 g, 10.8 mmol), benzyl bromide (0.86 ml, 7.9 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (3 x 50 mL). The organic layers were combined, washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the crude product. The crude product was recrystallized with ether to give the title compound as a light yellow solid (0.88 g, 53% yield).