Sodium hydride → 2-(5-{3-(2-Fluoro-4-{[3-(tetrahydro-2H-pyran-2-yloxy)azetidin-1-yl]carbonyl}phenoxy)-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-1H-pyrrol-2-yl)-1,3-thiazole

HRID 1964571Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1964571
[OH:1][C:2]1[CH:3]=[C:4]([C:14]2[N:15](C(OC(C)(C)C)=O)[C:16]([C:19]3[S:20][CH:21]=[CH:22][N:23]=3)=[CH:17][CH:18]=2)[CH:5]=[C:6]([O:8][C@@H:9]([CH3:13])[CH2:10][O:11][CH3:12])[CH:7]=1.[F:31][C:32]1[CH:33]=[C:34]([CH:48]=[CH:49][C:50]=1F)[C:35]([N:37]1[CH2:40][CH:39]([O:41][CH:42]2[CH2:47][CH2:46][CH2:45][CH2:44][O:43]2)[CH2:38]1)=[O:36].[H-].[Na+]>CS(C)=O.[Cl-].[Na+].O>[F:31][C:32]1[CH:33]=[C:34]([C:35]([N:37]2[CH2:40][CH:39]([O:41][CH:42]3[CH2:47][CH2:46][CH2:45][CH2:44][O:43]3)[CH2:38]2)=[O:36])[CH:48]=[CH:49][C:50]=1[O:1][C:2]1[CH:3]=[C:4]([C:14]2[NH:15][C:16]([C:19]3[S:20][CH:21]=[CH:22][N:23]=3)=[CH:17][CH:18]=2)[CH:5]=[C:6]([O:8][C@@H:9]([CH3:13])[CH2:10][O:11][CH3:12])[CH:7]=1

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 66681373t-Butyl 2-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylateHCID 666832281-(3,4-difluorobenzoyl)-3-(tetrahydro-2H-pyran-2-yloxy)azetidine

Produkt 1

HCID 666808962-(5-{3-(2-Fluoro-4-{[3-(tetrahydro-2H-pyran-2-yloxy)azetidin-1-yl]carbonyl}phenoxy)-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-1H-pyrrol-2-yl)-1,3-thiazoleAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

t-Butyl 2-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate (150 mg, 0.348 mmol) synthesized in Example (38d) and 1-(3,4-difluorobenzoyl)-3-(tetrahydro-2H-pyran-2-yloxy)azetidine (220 mg, 0.740 mmol) synthesized in Example (42a) were dissolved in dimethyl sulfoxide (5.0 mL), and sodium hydride (60%, 70 mg, 1.75 mmol) was added, followed by stirring at 100° C. for 1.5 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, saturated brine (30 mL) was added, and extraction was carried out with ethyl acetate (30 mL). Subsequently, drying was carried out over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=65%-85%) to afford the desired compound (158 mg, yield 75%) as a white solid.

Aufarbeitung

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionextraction
  3. customSubsequently, drying
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe resulting residue was purified
  6. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=65%-85%)

Quellen und Nachweise

ORD-Eintrag
ord-7bbc4ab74eda4b7396c2332d6b190a96
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08415359B2

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