4-Methylmorpholine → N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-2-butylnorleucine

Participants

Reaction Steps

N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine (0.020 g, 0.037 mmol) and NMM (0.040 ml, 0.363 mmol) were dissolved in DCM (5 ml) at 30° C. TBTU (a total of 0.016 g, 0.050 mmol) were added in portions and the mixture was stirred for 1 h. 2-Butylnorleucine (0.007 g, 0.037 mmol) was added and the mixture was stirred at 30° C. for 18 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by preparative HPLC, using a gradient of 20-50% MeCN in 0.1M ammonium acetate buffer as eluent. After freeze-drying, 0.009 g (34% yield) of the title product was obtained as a white solid. M/z: 710.1. 1H NMR (DMSO, 400 MHz): δ 0.73-0.82 (m, 6H), 0.88-1.22 (m, 8H), 1.56-1.69 (m, 2H), 1.96-2.07 (m, 2H), 3.71 (d, 2H), 4.32 (d, 1H), 4.36 (ABq, 2H), 4.52 (s, 2H), 5.16 (d, 1H), 6.95-7.01 (m, 2H), 7.11-7.26 (m, 4H), 7.30-7.40 (m, 4H), 7.61 (s, 1H), 7.98-8.06 (m, 2H), 8.25-8.42 (m, 1H).

Provenance & Evidence