反应详情

4-Amino-2-phenylbenzoyl methionine methyl ester hydrochloride (compound 8, 111.8 mg, 0.2833 mmol) and N-methylimidazole-4-yl-acetic acid hydrochloride (50 mg, 0.2832 mmol) were suspended in 10 mL of methylene chloride. To this solution was added diisopropylethylamine (197 μL, 4.0 eq) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (107.4 mg, 0.2833 mmol). After stirring at ambient temperature for 2 days, the reaction was worked up by washing with dilute HCl (PH=3.0) and concentrated sodium bicarbonate. After evaporating solvents, the residue was purified by flash column chromatography (CH2Cl2-Methanol, 10:1) to give [4-(1-Methylimidazole-4-ylacetamido)-2-phenylbenzoyl]methionine methyl ester (106 mg, 78%); m.p. 69-70° C.; 1H NMR (CDCl3) δ 9.89 (s, 1H, amide), 7.67 (d, J=8.4 Hz, 1H), 7.60 (d, J=8.4 Hz, 1H), 7.55 (s, 1H), 7.46 (s, 1H, imidazole), 7.34-7.42 (m, 5H), 6.81 (s, 1H, imidazole), 5.90 (d, J=7.7 Hz, 1H, amide), 4.63 (ddd, J=5.1, 7.3 and 7.7 Hz, 1H, Met α H), 3.72 (s, 3H, OCH3), 3.64 (s, 5H, N-methyl and imidazole acetyl), 2.10 (t, J=7.6 Hz, 2H), 1.98 (s, 3H), 1.83-1.94 (m, 1H), 1.66-1.75 (m, 1H); 13C NMR (CDCl3) δ 171.7, 169.0, 168.9, 140.3, 140.1, 139.8, 137.3, 135.3, 129.6, 129.3, 128.5, 128.3, 127.5, 120.6, 118.5, 118.0, 52.1, 51.6, 36.3, 33.3, 30.8, 29.4, 15.0; LRMS (EI) for C25H28O4N4S 480 (M+, 20), 406 (100), 318 (50); HRMS (EI) calcd 480.1813, obsd 480.1829.

1. washby washing with dilute HCl (PH=3.0) and concentrated sodium bicarbonate
2. customAfter evaporating solvents
3. customthe residue was purified by flash column chromatography (CH2Cl2-Methanol, 10:1)