反应详情

温度

60 °C

4-({Acetyl[(1-methyl-1H-1,2,3-triazol-4-yl)methyl]amino}methyl)benzoic acid (17.7 mg, 0.061 mmol), 1,1-dimethylethyl[2-({[4-(chloromethyl)phenyl]carbonyl}amino)-4-(2-thienyl)phenyl]carbamate (22 mg, 0.074 mmol), HOBT (11 mg, 0.074 mmol) and EDC (12 mg, 0.074 mmol) were taken into DMF (409 ul) and stirred at 60° C. overnight. The reaction was diluted with EtOAc and washed with ½ saturated NaHCO3 3×, brine, dried (MgSO4) and concentrated to afford a residue taken into ca 1 mL DCM:TFA (2:1) and stirred for 2 h. This solution was concentrated and purified via HPLC (20-100% MeCN in water with 0.025% TFA) to afford fractions poured into sat. aq. NaHCO3 and extracted with EtOAc 2×. The combined organic layers were washed with brine, dried (MgSO4) and concentrated to afford the requisite material as a dark tan solid. 1H NMR (d6-DMSO, 600 MHz, 90° C.) δ 9.46 (br s, 1H), 8.00-7.90 (m, 3H), 7.50 (d, J=2.1 Hz, 1H), 7.32 (d, J=8.2 Hz, 2H), 7.29 (dd, J=5.3, 1.2 Hz, 1H), 7.24 (dd, J=8.5, 2.3 Hz, 1H), 7.17 (dd, J=3.5, 1.2 Hz, 1H), 7.01 (dd, J=5.0, 3.5 Hz, 1H), 6.81 (d, J=8.2 Hz, 1H), 4.94 (br s, 2H), 4.66-4.54 (m, 3H), 4.50 (s, 2H), 3.98 (s, 2H), 2.24-2.00 (m, 3H). MS: cal'd 461 (MH+), exp 461 (MH+).

1. washwashed with ½ saturated NaHCO3 3×, brine
2. dry with materialdried (MgSO4)
3. concentrationconcentrated
4. customto afford a residue
5. stirringstirred for 2 h
6. concentrationThis solution was concentrated
7. custompurified via HPLC (20-100% MeCN in water with 0.025% TFA)
8. customto afford fractions
9. extractionextracted with EtOAc 2×
10. washThe combined organic layers were washed with brine
11. dry with materialdried (MgSO4)
12. concentrationconcentrated