反应详情

温度

0 °C

At 0° C. the solution of 746 mg (0.81 mmol) of HCl.Arg(Tos)-Pro-Ala-Lys(ClZ)-OBzl (SEQ ID NO: 12) in 50 ml of anhydrous tetrahydrofuran was adjusted to pH 9, to which the pre-cold solution of 340 mg (0.82 mmol) of Boc-Lys(ClZ)-OH, 110 mg (0.82 mmol) of 1-hydroxybenzotriazole and 170 mg (0.82 mmol) of dicyclohexylcarbodiimide in 40 ml of anhydrous tetrahydrofuran was added. The reaction mixture was stirred at 0° C. for 2 h and at room temperature for 16 h and TLC (chloroform/methanol, 10:1) indicated complete disappearance of HCl.Arg(Tos)-Pro-Ala-Lys(ClZ)-OBzl (SEQ ID NO: 12). The resulted precipitates of N,N-dicyclohexylurea were filtrated and the filtrate was diluted with 100 ml of ethyl acetate. The solution obtained was washed successively with saturated NaCO3 in water (50 ml×3), saturated NaCl in water (50 ml×3) and KHSO4 in water (5%, 50 ml×3). The separated ethyl acetate layer was dried with anhydrous MgSO4, and then evaporated. The residue was purified on sinica gel chromatography (CHCl3/CH3OH, 30/1) to provide 850 mg (81%) of the title compound as a glassy mass. Mp 78–88° C., FAB-MS (m/e) 1111.3[M+H]+, 1132.5[M+Na]+, 1010.0[M-Boc]+.

1. customAt 0° C.
2. additionwas added
3. customThe resulted precipitates of N,N-dicyclohexylurea
4. filtrationwere filtrated
5. additionthe filtrate was diluted with 100 ml of ethyl acetate
6. customThe solution obtained
7. washwas washed successively with saturated NaCO3 in water (50 ml×3), saturated NaCl in water (50 ml×3)
8. dry with materialThe separated ethyl acetate layer was dried with anhydrous MgSO4
9. customevaporated
10. customThe residue was purified on sinica gel chromatography (CHCl3/CH3OH, 30/1)