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

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).

1. customThe reaction solvent was removed in vacuo
2. dissolutionthe residue was dissolved in ethyl acetate
3. customThe solution was transferred to a separatory funnel
4. washwashed twice with 1N sodium hydrogen sulfate
5. extractionThe combined aqueous layers were extracted with ethyl acetate
6. washThe combined organic layers were washed with 5% aqueous potassium carbonate and brine
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. customevaporated in vacuo
10. customThe residue was purified on a preparative TLC plate (20×20 cm, 1000 μM)
11. washeluting with 97:3 chloroform
12. customThe product band was removed
13. washeluted with 3:1 methylene chloride
14. filtrationmethanol, filtered
15. customevaporated in vacuo
16. customThe residue was triturated with hexane and diethyl ether
17. customThe slurry was evaporated in vacuo to a residue
18. customdried under high vacuum

ORD 기록

ord-54829210415e4ca7b0d2720829bb4ebf

출처 데이터셋

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07419967B2