Acetone → (2R,4R)-5-(5'-Chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-{[1-((S)-2-methoxycarbonylamino-3-methylbutyryloxymethoxy)-1H-[1,2,3]triazole-4-carbonyl]amino}pentanoic Acid

HRID 516473Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 516473
Cl[CH2:2][O:3][C:4](=[O:14])[C@@H:5]([NH:9][C:10]([O:12][CH3:13])=[O:11])[CH:6]([CH3:8])[CH3:7].[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([F:45])=[C:20]([C:22]2[CH:27]=[CH:26][C:25]([CH2:28][C@@H:29]([NH:36][C:37]([C:39]3[N:40]=[N:41][N:42]([OH:44])[CH:43]=3)=[O:38])[CH2:30][C@@H:31]([OH:35])[C:32]([OH:34])=[O:33])=[CH:24][CH:23]=2)[CH:21]=1.CC(C)=O.CCN(CC)CC>>[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([F:45])=[C:20]([C:22]2[CH:27]=[CH:26][C:25]([CH2:28][C@@H:29]([NH:36][C:37]([C:39]3[N:40]=[N:41][N:42]([O:44][CH2:2][O:3][C:4](=[O:14])[C@@H:5]([NH:9][C:10]([O:12][CH3:13])=[O:11])[CH:6]([CH3:8])[CH3:7])[CH:43]=3)=[O:38])[CH2:30][C@@H:31]([OH:35])[C:32]([OH:34])=[O:33])=[CH:24][CH:23]=2)[CH:21]=1

Komponenten

5

Edukt 4

HCID 180AcetoneHCID 8471TriethylamineHCID 67969390(2R,4R)-5-(5'-Chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-[(1-hydroxy-1H-[1,2,3]triazole-4-carbonyl)amino]pentanoic AcidHCID 86669865(S)-chloromethyl 2-((methoxycarbonyl)amino)-3-methylbutanoate

Produkt 1

HCID 86705161(2R,4R)-5-(5'-Chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-{[1-((S)-2-methoxycarbonylamino-3-methylbutyryloxymethoxy)-1H-[1,2,3]triazole-4-carbonyl]amino}pentanoic AcidAusbeute 7,7 %

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

(S)-2-Methoxycarbonylamino-3-methylbutyric acid chloromethyl ester (37.4 mg, 167 μmol) was added to a solution of (2R,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxy-4-[(1-hydroxy-1H-1,2,3-triazole-4-carbonyl)amino]pentanoic acid (30.0 mg, 66.8 mol) in acetone (0.5 mL, 6.8 mmol). Et3N (18.6 μL, 134 μmol) was added and the resulting mixture was stirred at 65° C. for 2 hours. The mixture was then concentrated in vacuo to yield a yellow liquid. The crude liquid was purified (preparative scale C18 column chromatography, small column, using 30-90% MeCN in water with 0.05% TFA) to yield the title compound as a white solid (8.2 mg). MS m/z [M+H]+ calc'd for C28H31ClFN5O9, 636.18. found 636.1.

Aufarbeitung

  1. concentrationThe mixture was then concentrated in vacuo
  2. customto yield a yellow liquid
  3. customThe crude liquid was purified (preparative scale C18 column chromatography, small column, using 30-90% MeCN in water with 0.05% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-c45f9ddf3d564a7d9f5f5527788e0d5d
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108934B2

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