反应详情

[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-acetic acid (96 mg, 0.20 mmol), prepared as in Reference 9, was dissolved in dry N,N-dimethylformamide (20 mL) and the solution was treated with O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (84 mg, 0.22 mmol) and 2,3,4-trimethyl-pyridine (0.106 mL, 0.80 mmol). The mixture was stirred for one hour and then 4-(2-aminoethyl)-morpholine (29 uL, 0.22 mmol) was added. The mixture was stirred until the reaction was complete (½ to 1 hours) and then neutralizated with 1N hydrochloric acid to pH˜3. The solvents were evaporated at 30° C. to give an oily residue. The crude amide then was prepped at 2:30 (acetonitrile/20 mmol HCl) and the solvents were lyophilized to give 2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-sulfamoyl-biphenyl-3-yl]-N-(2-morpholin-4-yl-ethyl)-acetamide (63.0 mg, 53%). LCMS: (MH+)=594.3; (MH−)=592.2. NMR (DMSO-d6) d 2.78 (m, 4H), 3.12 (m, 2H), 3.26 (t, J=3 Hz, 2H), 3.57 (m, 4H), 3.59 (s, 2H), 7.17 (d, J=5 Hz, 1H), 7.23 (br s, 1H), 7.37 (d, J=1.5 Hz, 1H), 7.70 (m, 2H), 7.79 (d of d, J=1.5 Hz, 1H), 7.88 (d, J=5 Hz, 1H), 8.22 (d, J=1 Hz, 1H), 8.24 (s, 1H), 8.59 (t, J=3 Hz, 1H), 9.18, 9.43 (2s, 4H).

1. stirringThe mixture was stirred until the reaction
2. custom(½ to 1 hours)
3. customThe solvents were evaporated at 30° C.
4. customto give an oily residue