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 909501ノート

反応式

HRID 909501 の反応式
[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

参加物

6

反応物 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

生成物 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-thiazole収率 75%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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%)

出典と根拠

ORDレコード
ord-bab59435c3ea478685f7ea837aaf8607
出典データセット
uspto-grants-2011_09
特許番号
US08017610B2

反応ノート

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