1-Hydroxybenzotriazole → HCID 11202234, compound

Participants

Reaction Steps

To a solution of (E)-(S)-4-(3-biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (Example 19, step A) (0.30 g, 0.78 mmol), N-isopropyl-ethane-1,2-diamine (0.087 g, 0.85 mmol) and HOBt (0.16 g, 1.16 mmol) in DMF (7.8 mL), was added EDCl (0.22 g, 1.16 mmol). The resulting solution was stirred under N2 at rt for 20 h. The solution was diluted with H2O (50 mL) and extracted with 3:1 EtOAc/iPrOH (3×60 mL). The combined organic extracts were washed with 1 N NaOH (1×50 mL) and brine (75 mL), dried (Na2SO4) and filtered, and the solvent was removed. The residue was purified by column chromatography on silica gel using a gradient of 2–10% (MeOH (1% NH4OH)/CH2Cl2 to afford 0.18 g (51%) of the desired product as a white solid. Rf=0.26 (10% MeOH (1% NH4OH)/CH2Cl2). MS (electrospray): mass calculated for C29H34N4O2, 470.27; m/z found, 471.3 [M+H]+, 493.2 [M+Na]+, 941.5 [2M+H]+. 1H NMR (400 MHz, CDCl3): 8.10 (s, 1H), 7.48 (d, J=7.5 Hz, 2H), 7.43 (d, J=8.5 Hz, 2H), 7.39–7.33 (m, 5H), 7.31–7.25 (m, 3H), 7.21 (d, J=7.24 Hz, 2H), 6.76 (dd, J=15.3, 5.7 Hz, 1H), 6.25 (d, J=8.3 Hz, 1H), 6.00 (d, J=15.3 Hz, 1H), 4.86–4.79 (m, 1H), 3.46–3.41 (m, 1H), 3.31–3.27 (m, 1H), 2.95–2.85 (m, 2H), 2.77–2.67 (m, 3H), 1.01 (d, J=6.0 Hz, 6H).

Provenance & Evidence