1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-(4-Aminobenzyl)-3-(3-(3-hydroxyphenyl)-1-morpholino-1-oxopropan-2-yl)urea

Participants

Reaction Steps

Acid derivative 175 (1 equivalent) was dissolved in 2 ml of DMF. Amine (1.1 equivalent), Hydroxybenzotriazole (HOBO (1.2 equivalent), diisopropylethylamine (DIEA) (2.2 equivalent) and 1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide (EDAP) (1.2 equivalent) were added successively and the reaction mixture is stirred for 20 h at room temperature. The reaction mixture is concentrated and 100 ml of AcOEt are added. The organic phase are washed with NaHCO3 saturated, 10% citric acid and brine then dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (AcOEt) to afford the amide as white solid (80 mg, 73%). 1H NMR (DMSO): δ 1.48 (s, 9H), 1.60 (m, 2H), 1.72 (m, 2H), 2.62 (m, 1H), 2.80 (dd, 1H, J=13.4, 5.2 Hz), 3.77 (m, 2H), 3.98 (m, 2H), 4.08 (d, 2H, J=5.3 Hz), 4.90 (m, 1H), 6.14 (d, 1H, J=8.8 Hz), 6.43 (t, 1H, J=5.3 Hz), 6.60 (m, 3H), 7.05 (d, 1H, J=8.5 Hz), 7.08 (d, 2H, J=8.2 Hz), 7.36 (d, 2H, J=8.2 Hz), 9.25 (s, 1H), 9.27 (s, 1H). The protected urea (78 mg) was dissolved in 2 μl of DCM and 2 ml of TFA was added then the reaction mixture was let 1 h at room temperature. The reaction mixture was concentrated and purified by precipitation using AcOEt/Hexane to afford the urea deprotected 176 as yellow solid (75 mg, 92%). HPLC method B tr=15.77 mn (92.3%). ESI-MS m/z: 399.4 [M+H]+.

Provenance & Evidence