1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-[3-(3-Methyl-1-{2-[4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-butyl)-isoxazol-5-yl]-propionic acid methyl ester

Participants

Reaction Steps

To a stirred solution of [4-(3-o-tolyl-ureido)-phenyl]-acetic acid (305 mg, 1.07 mmol), DIEA (1.3 ml), HOBT (120 mg, 0.89 mmol) and EDCI (170 mg, 0.89 mmol) in CH2Cl2 (8 ml) at room temperature was added a solution of 3-[3-(1-amino-3-methyl-butyl)-isoxazol-5-yl]-propionic acid methyl ester hydrobromide (272 mg, 0.85 mmol) in CH2Cl2 (12 ml). After stirring for 16 h at room temperature the mixture was diluted with CH2Cl2 (20 ml) and poured into water. The layers were separated and the aqueous layer was extracted with CH2Cl2 (20 ml×3). The combined organics were dried over MgSO4; filtered; and concentrated under reduced pressure. The residue was purified by Flash 40 chromatography using a silica gel column and eluting with 65% EtOAc/hexane to give 220 mg of the title compound as a white amorphous solid. MP 153-4° C.; MS [+1]+507.2; 1H nmr (400 MHz, CDCl3) δ0.88 (d, J=6.4 Hz, 6H), 1.53-1.66 (m, 3H), 2.21 (s, 3H), 2.66 (t, J=7.6 Hz, 2H), 3.00 (t, J=7.6 Hz, 2H), 3.49 (s, 2H), 3.68 (s, 3H), 5.15 (dt, J=6.2 and 8.7 Hz, 1H), 5.85 (s, 1H), 6.11 (d, J=8.5 Hz, 1H), 6.65 (s, 1H), 7.00 (s, 1H), 7.05-7.24 (m, 7H), 7.53 (d, 1H); Anal. calcd. for C28H34N4O5: C (66.39), H (6.76), N (11.05). Found: C (66.29), H (7.11), N (11.11).

Provenance & Evidence