1-Hydroxybenzotriazole → N-tert-Butoxycarbonyl-trans-4-(N-tert-Butoxycarbonylglycylamino)-D-Prolyl-trans-4-((R)-2-Hydroxy-4-Phenylbutyrylamino)-L-proline 3-Quinolylamide

Participants

Reaction Steps

Triethylamine (40 μL), 1-hydroxybenzotriazole (36 mg), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (55 mg) were added to a solution of N-tert-butoxycarbonyl-trans-4-(N-tert-butoxycarbonylglycylamino)-D-proline (F, 112 mg) and trans-4-((R)-2-hydroxy-4-phenylbutyrylamino)-L-proline 3-quinolylamide (Compound D101 (H), 100 mg) in dichloromethane (10 mL) at 0° C. The mixture was stirred at room temperature for 18 hr and evaporated in vacuo. The residue was diluted with ethyl acetate and washed with 1 N hydrochloric acid, water, saturated sodium hydrogen carbonate, and brine. The organic layer was dried over anhydrous sodium sulfate and evaporated in vacuo. The residue was purified by silica gel column chromatography (methanol:chloroform=1:50 to 1:20, v/v) to give the title compound (124 mg) as a colorless solid: 1H NMR (400 MHz, CDCl3) δ 1.34-1.44 (m, 18H), 1.86-1.92 (m, 1H), 2.03-2.14 (m, 1H), 2.21-2.64 (m, 3H), 2.71-2.75 (m, 2H), 3.33-3.75 (m, 4H), 3.94-4.10 (m, 2H), 4.21-4.78 (m, 3H), 7.14-7.27 (m, 5H), 7.51-7.71 (m, 2H), 7.83-7.99 (m, 2H), 8.70-8.72 (m, 1H), and 8.96-9.05 (m, 1H).

Provenance & Evidence