Reaktion #738527

Reaktionsgleichung

N,N′-diisopropylcarbodiimide

dimethylformamide piperidine

1-hydroxybenzotriazole

(8-naphthalen-1-ylmethyl-4-oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-3-yl)-acetic acid

1-hydroxybenzotriazole

N,N′-diisopropylcarbodiimide

→

desired product

2-(S)-[2-(8-Naphthalen-1-ylmethyl-4-oxo1-phenyl-1,3,8-triaza-spiro[4.5]dec-3-yl)-acetylamino]-5ureido-pentanoic acid amide

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe resin was filtered
2. 2
   Waschenrinsed with dimethylformamide (8 ml)
3. 3
   workup.STIRRINGshaken for 30 min at room temperature
4. 4
   Waschenthe resin was washed
5. 5
   workup.WAITto shake for 20 h at room temperature
6. 6
   FiltrationThe resin was filtered
7. 7
   Waschenwashed
8. 8
   workup.STIRRINGshaken for 30 min at room temperature
9. 9
   FiltrationThe resin was filtered
10. 10
    Waschenrinsed with dimethylformamide (8 ml)
11. 11
    workup.STIRRINGshaken for 30 min at room temperature
12. 12
    Waschenthe resin was washed
13. 13
    workup.WAITto shake at room temperature for 20 h
14. 14
    Filtrationfiltered
15. 15
    Temperaturheated to 40° C. for 1 h
16. 16
    FiltrationThe resin was again filtered
17. 17
    Temperaturheated to 40° C. for an additional 1 h
18. 18
    FiltrationThe resin was filtered
19. 19
    Waschenwashed
20. 20
    Trocknen3×dichloromethane (8 ml) and air-dried
21. 21
    workup.ADDITIONThe resin was treated with trifluroacetic acid/water (95/5) (8 ml) for 2 h at room temperature
22. 22
    SonstigeThe filtrate was collected
23. 23
    Einengenconcentrated in vacuo

Vorschrift

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.

Quelle