Reaktion #57453

Reaktionsgleichung

N1-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N1-(cyclopentyloxy)-4-methoxy-1-benzenesulfonamide

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

N-hydroxybenzotriazole

(2S)-4-amino-4-oxo-2-[(2-quinolinylcarbonyl)amino]butanoic acid hydrochloride

N,N-diisopropylethylamine

→

(2S)-N1-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)-2-[(2-quinolinylcarbonyl)amino]butanediamide

Ausbeute 41.4%

Lösungsmittel

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction solvent was removed in vacuo
2. 2
   workup.DISSOLUTIONthe residue was dissolved in ethyl acetate
3. 3
   SonstigeThe solution was transferred to a separatory funnel
4. 4
   Waschenwashed twice with 1N sodium hydrogen sulfate
5. 5
   ExtraktionThe combined aqueous layers were extracted with ethyl acetate
6. 6
   WaschenThe combined organic layers were washed with 5% aqueous potassium carbonate and brine
7. 7
   Trocknendried over anhydrous magnesium sulfate
8. 8
   Filtrationfiltered
9. 9
   Sonstigeevaporated in vacuo
10. 10
    SonstigeThe residue was purified on a preparative TLC plate (20×20 cm, 1000 μM)
11. 11
    Wascheneluting with 97:3 chloroform
12. 12
    SonstigeThe product band was removed
13. 13
    Wascheneluted with 3:1 methylene chloride
14. 14
    Filtrationmethanol, filtered
15. 15
    Sonstigeevaporated in vacuo
16. 16
    SonstigeThe residue was triturated with hexane and diethyl ether
17. 17
    SonstigeThe slurry was evaporated in vacuo to a residue
18. 18
    Sonstigedried under high vacuum

Vorschrift

A mixture of N1-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N1-(cyclopentyloxy)-4-methoxy-1-benzenesulfonamide (Step 1, Example 48), (73 mg, 0.168), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (34 mg, 0.18 mmol), N-hydroxybenzotriazole (24 mg, 0.18 mmol), and (2S)-4-amino-4-oxo-2-[(2-quinolinylcarbonyl)amino]butanoic acid hydrochloride (57 mg, 0.18 mmol, Eur. Pat. Appl. EP 432694) was combined under an Argon atmosphere at ambient temperature in anhydrous dimethylformamide (2 mL). After addition of N,N-diisopropylethylamine (896 μL, 0.513 mmol), the mixture was stirred for 16 hours. The reaction solvent was removed in vacuo and the residue was dissolved in ethyl acetate. The solution was transferred to a separatory funnel and washed twice with 1N sodium hydrogen sulfate. The combined aqueous layers were extracted with ethyl acetate. The combined organic layers were washed with 5% aqueous potassium carbonate and brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The residue was purified on a preparative TLC plate (20×20 cm, 1000 μM) eluting with 97:3 chloroform:methanol. The product band was removed, eluted with 3:1 methylene chloride:methanol, filtered, and evaporated in vacuo. The residue was triturated with hexane and diethyl ether. The slurry was evaporated in vacuo to a residue and dried under high vacuum to provide (2S)-N1-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)-2-[(2-quinolinylcarbonyl)amino]butanediamide (49 mg, 41%) as a white solid. H1-NMR (chloroform-D3): 1.52 (m, 4H), 1.75 (m, 4H), 2.82 (m, 5H), 3.10 (m, 1H), 3.82 (b, 1H), 3.84 (s, 3H), 3.91 m, 1H), 4.29 (m, 1H), 4.78 (m, 1H), 4.95 (m, 1H), 5.76 (b, 1H), 6.22 (b, 1H), 7.00 (m, 5H), 7.12 (d, 2H), 7.22 (d, 1H), 7.60 (m, 1H), 7.75 (m, 3H), 7.83 (d, 1H), 8.14 (m, 2H), 8.25 (d, 1H), 9.15 (d, 1H). MS(ESI): 704 (M+H).

Quelle