Sodium Iodide → Butyric acid (R)-3-[N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionyloxymethyl Ester

HRID 541521Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 541521
[C:1]([O:6][CH2:7]Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[Na+].[I-].[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([F:42])=[C:16]([C:18]2[CH:23]=[CH:22][C:21]([CH2:24][N:25]([CH2:36][C@@H:37]([OH:41])[C:38]([OH:40])=[O:39])[NH:26][C:27]([C:29]3[O:33][N:32]=[C:31]([O:34][CH3:35])[CH:30]=3)=[O:28])=[CH:20][CH:19]=2)[CH:17]=1.CCN(C(C)C)C(C)C>CC(C)=O.C(O)(=O)C>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([F:42])=[C:16]([C:18]2[CH:19]=[CH:20][C:21]([CH2:24][N:25]([CH2:36][C@@H:37]([OH:41])[C:38]([O:40][CH2:7][O:6][C:1](=[O:5])[CH2:2][CH2:3][CH3:4])=[O:39])[NH:26][C:27]([C:29]3[O:33][N:32]=[C:31]([O:34][CH3:35])[CH:30]=3)=[O:28])=[CH:22][CH:23]=2)[CH:17]=1

Komponenten

7

Edukt 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 2725008Chloromethyl butanoateHCID 67972936(R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic Acid

Produkt 1

HCID 86705099Butyric acid (R)-3-[N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionyloxymethyl EsterAusbeute 26,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 180AcetoneLösungsmittel2×

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

A mixture of chloromethyl butyrate (16.2 μL, 129 μmol) and NaI (19.4 mg, 129 μmol) in acetone (0.7 mL, 10 mmol) was heated at 65° C. for 1 hour. The mixture was then cooled to room temperature and a mixture of (R)-3-[N-(5′-Chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid (20.0 mg) and DIPEA (15.0 mL, 0.1 mmol) in acetone (0.3 mL) was added. The resulting mixture was stirred at room temperature for 1 hour then concentrated. The residue was dissolved in AcOH (2.0 mL), filtered, and purified by reverse phase preparative HPLC. The desired fractions were combined and freeze dried to yield a white solid. The solid was dissolved in acetic acid (1.5 mL), filtered and purified by reverse phase preparative HPLC to yield the title compound (6.5 mg, purity 100%). MS m/z [M+H]+ calc'd for C26H27ClFN3O8, 564.15. found. 564.

Aufarbeitung

  1. temperatureThe mixture was then cooled to room temperature
  2. additionwas added
  3. concentrationthen concentrated
  4. dissolutionThe residue was dissolved in AcOH (2.0 mL)
  5. filtrationfiltered
  6. custompurified by reverse phase preparative HPLC
  7. customfreeze dried
  8. customto yield a white solid
  9. filtrationfiltered
  10. custompurified by reverse phase preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-3fca85e3727b40fd9c479850b42643c4
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08871792B2

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