55 mg (0.16 mmol) of 3-[5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2,4-dimethyl-1H-pyrrol-3-yl]-propionic acid methyl ester were dissolved in DMF (5 mL). Subsequently 103 mg (2 equiv.) of Cs2CO3 and 65.8 mg (1.5 equiv.) of 3-bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole were added and the resulting mixture was stirred for 4 h at 800 C. Because of low conversion 206 mg (4 equiv.) of Cs2CO3 were added stirring was continued for 7 h at 80° C. The reaction mixture was acidified by the addition of acetic acid and concentrated. The residue was purified by preparative HPLC(CH3CN/H2O gradient+0.05% formic acid) to give 3-[1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2,4-dimethyl-1H-pyrrol-3-yl]-propionic acid methyl ester (34 mg) as a colorless amorphous material. MS (ESI+): m/e=548 [M+H]+, chloro pattern.
