Diisopropylcarbodiimide → HCID 59965703, compound

Rink Amide (AM) resin (Novabiochem) (0.200 g, 0.138 mmol) was suspended in dimethylformamide/piperidine (80/20) (8 ml) and shaken for 30 min at room temperature. The resin was filtered and rinsed with dimethylformamide (8 ml) and again suspended in dimethylformamide/piperidine (80/20) (8 ml) and shaken for 30 min at room temperature; the resin was washed as follows: 3×dimethylformamide/water (90/10) (8 ml), 3×dimethylformamide (8 ml), 3×dichloromethane (8 ml). The resin was suspended in dimethylformamide (8 ml), Fmoc-L-2-amino-5-ureido-n-valeric acid (L-Fmoc-Cit-OH) (0.227 g, 0.552 mmol) and 1-hydroxybenzotriazole (0.085 g, 0.552 mmol) were added. N,N′-diisopropylcarbodiimide (0.071 g, 0.552 mmol) was added and the reaction was allowed to shake for 20 h at room temperature. The resin was filtered and washed as follows: 3×dimethylformamide/water (90/10) (8 ml), 3×dimethylformamide (8 ml), 3×dichloromethane (8 ml). The resin was suspended in dimethylformamide/piperidine (80/20) (8 ml) and shaken for 30 min at room temperature. The resin was filtered and rinsed with dimethylformamide (8 ml) and again suspended in dimethylformamide/piperidine (80/20) (8 ml) and shaken for 30 min at room temperature; the resin was washed as follows: 3×dimethylformamide/water (90/10) (8 ml), 3×dimethylformamide (8 ml), 3×dichloromethane (8 ml). The resin was suspended in dimethylformamide (8 ml); (8-naphthalen-1-ylmethyl-4-oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-3-yl)-acetic acid (0.269 g, 0.552 mmol), 1-hydroxybenzotriazole (0.085 g, 0.552 mmol) and N,N′-diisopropylcarbodiimide (0.071 g, 0.552 mmol) were added. The reaction mixture was allowed to shake at room temperature for 20 h and filtered. The resin was suspended in dimethylsulfoxide (8 ml) and heated to 40° C. for 1 h. The resin was again filtered, suspended in dimethylsulfoxide (8 ml) and heated to 40° C. for an additional 1 h. The resin was filtered and washed as follows: 3×dimethylformamide/water (90/10) (8 ml); 3×dimethylformamide (8 ml); 3×dichloromethane (8 ml) and air-dried. The resin was treated with trifluroacetic acid/water (95/5) (8 ml) for 2 h at room temperature. The filtrate was collected and concentrated in vacuo to give the desired product.

1. filtrationThe resin was filtered
2. washrinsed with dimethylformamide (8 ml)
3. stirringshaken for 30 min at room temperature
4. washthe resin was washed
5. waitto shake for 20 h at room temperature
6. filtrationThe resin was filtered
7. washwashed
8. stirringshaken for 30 min at room temperature
9. filtrationThe resin was filtered
10. washrinsed with dimethylformamide (8 ml)
11. stirringshaken for 30 min at room temperature
12. washthe resin was washed
13. waitto shake at room temperature for 20 h
14. filtrationfiltered
15. temperatureheated to 40° C. for 1 h
16. filtrationThe resin was again filtered
17. temperatureheated to 40° C. for an additional 1 h
18. filtrationThe resin was filtered
19. washwashed
20. dry with material3×dichloromethane (8 ml) and air-dried
21. additionThe resin was treated with trifluroacetic acid/water (95/5) (8 ml) for 2 h at room temperature
22. customThe filtrate was collected
23. concentrationconcentrated in vacuo

ORD record

ord-1fbfca0d98794ccb8c133912589b9a27

Source dataset

uspto-grants-2001_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06277991B1