反应详情

温度

0 °C

To a suspension of N-methylsulfonyl-D-phenylalanyl-proline (497 mg, 1.46 mmol), 4-(aminomethyl)-1-piperidinecarboximidamide (470 mg, 1.9 mmol) and HOBt (217 mg, 1.6 mmol) in 1:1 v/v isopropyl alcohol/water (4.5 mL) was added NMM (0.32 mL, 2.9 mmol). The homogeneous solution was cooled to 0° C. and ethyl-3-(3-dimethylamino)-propylcarbodiimide·hydrochloride salt (EDAC·HCl) (308 mg, 1.6 mmol) was added. After 18 hr the reaction was concentrated in vacuo, dissolved in water (10 mL) and washed with ether (2×75 mL). Aqueous NaOH (1 N, 3.8 mL) was added until the aqueous layer attained pH 9.7, the aqueous layer was washed with ether (75 mL) and the process repeated. Aqueous HCl (1N, 3.8 mL) was added until the pH reached 2.0, the aqueous layer was washed with ethyl acetate (3×75 mL), concentrated in vacuo, dissolved in water, and lyophilized to give a foam which was subjected to chromatography on HP-20 polystyrene resin to provide the title compound (629 mg, 84%).

1. concentrationAfter 18 hr the reaction was concentrated in vacuo
2. dissolutiondissolved in water (10 mL)
3. washwashed with ether (2×75 mL)
4. additionAqueous NaOH (1 N, 3.8 mL) was added until the aqueous layer
5. washthe aqueous layer was washed with ether (75 mL)
6. additionAqueous HCl (1N, 3.8 mL) was added until the pH
7. washthe aqueous layer was washed with ethyl acetate (3×75 mL)
8. concentrationconcentrated in vacuo
9. dissolutiondissolved in water
10. customto give a foam which