Sodium hydride → HCID 58065483, compound

HRID 1964590Notes

Reaction equation

HRID 1964590 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:31][C:32]1[CH:33]=[C:34]([S:39]([N:42]2[CH2:45][CH2:44][CH2:43]2)(=[O:41])=[O:40])[CH:35]=[CH:36][C:37]=1F.[H-].[Na+].[Cl-].[NH4+]>CN1CCCC1=O>[N:42]1([S:39]([C:34]2[CH:35]=[CH:36][C:37]([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:32]([F:31])[CH:33]=2)(=[O:41])=[O:40])[CH2:45][CH2:44][CH2:43]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 66681891HCID 66681891, compound

Product 1

HCID 58065483HCID 58065483, compoundYield 43.4%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

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 (65.0 mg, 0.151 mmol) synthesized in Example (38d) and 1-[(3,4-difluorophenyl)sulfonyl]azetidine (42.3 mg, 0.181 mmol) synthesized in Example (56a) were dissolved in N-methylpyrrolidone (5.0 mL), and sodium hydride (55%, 20 mg, 0.45 mmol) was added, followed by stirring at 100° C. for 4 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, a saturated aqueous ammonium chloride solution (20 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 twice using silica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-35%) to afford the desired compound (35.6 mg, yield 43%) as a white 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 twice using
  7. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-35%)

Sources & evidence

ORD record
ord-60f6c213f4324474a456011bddb9827e
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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