4-Methylmorpholine → HCID 66842855, compound

Participants

Reaction Steps

N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine (0.025 g, 0.046 mmol) was dissolved in DMSO (2 ml) at 30° C. N-Methylmorpholine (0.014 g, 0.139 mmol) and TBTU (0.018 g, 0.056 mmol) were added. After 1 h, D-glucosaminic acid (0.018 g, 0.092 mmol) and tetrabutylammoniumbromide (0.001 g, 0.005 mmol) were added. The mixture was stirred for 15 minutes. Additional TBTU (18 mg, 0.056 mmol) was added. After 30 minutes, approximately 30% amide formation had occurred. The reaction was quenched by the addition of 0.1M NH4OAc buffer (2 ml). The intermediate ketone was purified by preparative HPLC using an eluent of 0-50% CH3CN in 0.1M NH4OAc buffer and freeze-dried. MeOH (3 ml) and NABH4 (0.005 g, 0.139 mmol) were added. After 5 minutes, the reaction was quenched by the addition of 0.1M NH4OAc buffer (1 ml). Concentration of the mixture and purification by preparative HPLC using an eluent of 0-50% CH3CN in 0.1M NH4OAc buffer gave the title compound (0.005 g, 16%) as a colourless solid. M/z: 718.0 (M−1). 1H NMR [(CD3)2SO), 400 MHz] δ 2.82-2.94 (m, 2H), 3.34-3.56 (m, 4H), 3.76-3.80 (m, 2H), 3.87-3.90 (m, 1H), 4.07-4.11 (m, 1H), 4.27-4.32 (m, 1H), 4.52 (s, 2H), 4.68-4.76 (m, 1H), 5.02-5.05 (m, 1H), 6.97-7.39 (m, 12H), 7.63-7.70 (m, 1H), 8.28-8.35 (m, 1H).

Provenance & Evidence