反应详情

The DMF:DMSO-containing solution of H-Glu(OtBu)-Lys(Boc)-Lys(Boc)-Glu(OtBu)-Val-Val-Glu(OtBu)-Glu(OtBu)-Ala-Glu(OtBu)-Asn-OtBu (~23 mmol) from step (d) was combined with Z-Asp(OtBu)-Leu-Lys(Boc)-OH (IV, 18.6 g, 28.0 mmol, 1.2 eq.) and HOBt (10.62 g, 69.0 mmol, 3.0 eq.) added and the solution cooled to 0°. DCC (7.87 g, 38.0 mmol, 1.65 eq.) was added to the cold stirring (mechanical) reaction mixture and the pH was maintained at 7.5-8.0 by addition of N-methylmorpholine (~17 mL). Stirring proceeded for 1 h at 0° and 23 h at 25°. The resultant reaction mixture was poured into H2O (10 L) and stirred for 1.5 h. The product was collected by filtration, washed with H2O (5 L), dried and washed with MeOH using the centrifuge to separate the 2 layers. When all the dicyclohexylurea was removed the product was pooled and dried in vacuo to give 44.56 g (77.9%); mp >330°; [α] D25 -11.56° (c 1, TFE); Rf 0.16 (CHCl3 :MeOH:AcOH; 80-5-1); Rf 0.36 (CHCl3 :MeOH:TFE:AcOH; 85-10-2.5-1).

1. additionadded
2. temperaturethe solution cooled to 0°
3. custom(mechanical) reaction mixture
4. stirringStirring
5. customThe resultant reaction mixture
6. stirringstirred for 1.5 h
7. filtrationThe product was collected by filtration
8. washwashed with H2O (5 L)
9. customdried
10. washwashed with MeOH using the centrifuge
11. customto separate the 2 layers
12. customWhen all the dicyclohexylurea was removed the product
13. customdried in vacuo
14. customto give 44.56 g (77.9%)