4-Methylmorpholine → (R)-3-Cyclohexyl-2-[2-(2-{4-[(2R,3R)-3-[2-(2,3-dihydro-benzofuran-6-yl)-2-hydroxy-ethylsulfanyl]-1-(4-fluoro-phenyl)-4-oxo-azetidin-2-yl]-phenoxy}-acetylamino)-acetylamino]-propionic acid

Participants

Reaction Steps

To a solution of {4-[(2R,3R)-3-[2-(2,3-dihydro-benzofuran-6-yl)-2-oxo-ethylsulfanyl]-1-(4-fluoro-phenyl)-4-oxo-azetidin-2-yl]-phenoxy}-acetic acid (33 mg, 0.065 mmol) in DMF (3 mL) at RT was added N-methylmorpholine (22 μl, 0.198 mmol) and TBTU (22 mg, 0.069 mmol). The mixture was stirred for 30 min before (R)-2-(2-amino-acetylamino)-3-cyclohexyl-propionic acid (15 mg, 0.066 mmol) was added. After 2 h 30 min, the reaction was quenched by the addition of water (1 mL) The mixture was diluted with MeOH (1 mL) and then added NaBH4 (35 mg, 0.925 mmol). After 15 min, the reaction was quenched by the addition of 1M HCl (3 mL) and the resulting solution was purified by preparative HPLC using a gradient of 0-60% MeCN in a 0.1M ammonium acetate buffer as eluent. Freeze-drying of the pure fractions gave the desired product.

Provenance & Evidence