Sodium hydride → 2-(5-{3-[4-(Azetidin-1-ylcarbonyl)-2-(trifluoromethyl)phenoxy]-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-1H-pyrrol-2-yl)-1,3-thiazole

HRID 1964586Notes

Reaction equation

HRID 1964586 reaction equation
[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[C:32]1[CH:43]=[CH:42][C:35]([C:36]([N:38]2[CH2:41][CH2:40][CH2:39]2)=[O:37])=[CH:34][C:33]=1[C:44]([F:47])([F:46])[F:45].[H-].[Na+].[Cl-].[NH4+]>CS(C)=O>[N:38]1([C:36]([C:35]2[CH:42]=[CH:43][C:32]([O:1][C:2]3[CH:3]=[C:4]([C:14]4[NH:15][C:16]([C:19]5[S:20][CH:21]=[CH:22][N:23]=5)=[CH:17][CH:18]=4)[CH:5]=[C:6]([O:8][C@@H:9]([CH3:13])[CH2:10][O:11][CH3:12])[CH:7]=3)=[C:33]([C:44]([F:45])([F:46])[F:47])[CH:34]=2)=[O:37])[CH2:41][CH2:40][CH2:39]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 66681373t-Butyl 2-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylateHCID 666816671-[4-Fluoro-3-(trifluoromethyl)benzoyl]azetidine

Product 1

HCID 580654852-(5-{3-[4-(Azetidin-1-ylcarbonyl)-2-(trifluoromethyl)phenoxy]-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-1H-pyrrol-2-yl)-1,3-thiazoleYield 68.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

t-Butyl 2-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate (119 mg, 0.276 mmol) synthesized in Example (38d) and 1-[4-fluoro-3-(trifluoromethyl)benzoyl]azetidine (145 mg, 0.587 mmol) synthesized in Example (54a) were dissolved in dimethyl sulfoxide (8.0 mL), and sodium hydride (60%, 39 mg, 0.97 mmol) was added, followed by stirring at 100° C. for 2 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, a saturated aqueous ammonium chloride solution (30 mL) was added, and extraction was carried out with ethyl acetate (30 mL). The organic layer was washed with saturated brine, and subsequently dried 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=45%-60%) to afford the desired compound (105 mg, yield 68%) as a yellow solid.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionextraction
  3. washThe organic layer was washed with saturated brine
  4. dry with materialsubsequently dried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe resulting residue was purified
  7. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=45%-60%)

Sources & evidence

ORD record
ord-a03f52ab04bb4a60bc1cd084fb987f11
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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