反応 #166834

反応方程式

carbamic acid methyl ester

3,9-bis-[2-(pyrrolidin-2-yl)-3H-imidazol-4-yl]-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepine

MeOCO-Val-OH

HATU

DMF

diisopropylethylamine

→

(1-{2-[5-(9-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepin-3-yl)-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl]-2-methyl-propyl)-carbamic acid methyl ester

溶媒

EtOAc

反応条件

後処理

1. 1
   洗浄The organic phase was washed with 1 N NaOH solution, water, and brine
2. 2
   乾燥was dried with sodium sulfate
3. 3
   濃縮Concentration and purification by HPLC (0.1% TFA/CH3CN/0.1% TFA/H2O)

実験手順

1-{2-[5-(9-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepin-3-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester: To the solution of 3,9-bis-[2-(pyrrolidin-2-yl)-3H-imidazol-4-yl]-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepine (25 mg, 0.035 mmol) and MeOCO-Val-OH (13 mg, 0.074 mmol) in DMF (1.2 ml) was added HATU (28 mg, 0.074 mmol), followed by diisopropylethylamine (61 μl, 0.35 mmol). The mixture was stirred for 90 minutes and was diluted with EtOAc. The organic phase was washed with 1 N NaOH solution, water, and brine, and was dried with sodium sulfate. Concentration and purification by HPLC (0.1% TFA/CH3CN/0.1% TFA/H2O) gave (1-{2-[5-(9-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-6-methyl-6,7-dihydro-5H-dibenzo[c,e]azepin-3-yl)-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl]-2-methyl-propyl)-carbamic acid methyl ester (24 mg). m/z: 794.3 (M+H)+, 397.8 (M+2H)+/2. 1H NMR (CD3OD, 300 MHz) δ 8.0-7.9 (8 H, m), 5.27 (2 H, m), 4.3-4.2 (2 H, m), 4.2-3.8 (8 H, m), 3.66 (6 H, s), 3.08 (3 H, s), 2.7-2.5 (2 H, m), 2.4-1.9 (8 H, m), 0.94-0.90 (12 H, m).

出典