反应详情

The DMF:DMSO-containing solution of H-Glu(OtBu)-Val-Val-Glu(OtBu)-Glu(OtBu)-Ala-Glu(OtBu)-Asn-OtBu (~32 mmol) from Example 3 was combined with Z-Glu(OtBu)-Lys(Boc)-Lys(Boc)-OH, III, Ro 22-4541 (36.8 g, 46 mmol, 1.44 eq.) and HOBt (14.7 g, 96 mmol, 3 eq.) added and the solution cooled to 0°. DCC (10.9 g, 52 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 (21 mL). Stirring proceeded for 2 h at 0° and 21 h at 25°. The resultant gelatenous reaction mixture was poured into H2O (9.0 L) and stirred for 4 h. The product was collected by filtration, washed with H2O (8×500 mL), dried and washed with MeOH using the centrifuge to separate the 2 phases. When all the dicyclohexylurea was removed the product was combined and dried in vacuo to give 45.22 g (71.5 %); mp 312° dec; [α]D25 -18.20° (c 1, DMSO); [α]D25 -13.27° (c 1, TFE); Rf 0.81 (n-BuOH:AcOH:Pyr:H2O; 15-3-10-12); Rf 0.52 (CHCl3 :MeOH:AcOH; 85-10-5). Amino Acid Anal. (6M HCl, 110°, 24 h): Asp(1.04); Glu(5.04); Ala(1.02); Lys(1.90); Val (1.67).(a)Anal. calc. for C96H160N14O29 (1974.4): C, 58.40; H, 8.17; N, 9.93. Found: C, 57.84; H, 8.28; N, 9.94.

1. additionadded
2. temperaturethe solution cooled to 0°
3. custom(mechanical) reaction mixture
4. stirringStirring
5. stirringstirred for 4 h
6. filtrationThe product was collected by filtration
7. washwashed with H2O (8×500 mL)
8. customdried
9. washwashed with MeOH using the centrifuge
10. customto separate the 2 phases
11. customWhen all the dicyclohexylurea was removed the product
12. customdried in vacuo
13. customto give 45.22 g (71.5 %)