Pyrazole → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-bromo-6-(1H-pyrazol-1-yl)pyridin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 1508597Notes

Reaction equation

HRID 1508597 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([Br:26])=[CH:24][CH:23]=[C:22](Cl)[N:21]=3)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[NH:31]1[CH:35]=[CH:34][CH:33]=[N:32]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(OCC)(=O)C.[OH-].[Na+]>[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([Br:26])=[CH:24][CH:23]=[C:22]([N:31]4[CH:35]=[CH:34][CH:33]=[N:32]4)[N:21]=3)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 3

HCID 1048PyrazoleHCID 6101p-Toluenesulfonic acidHCID 57576268(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one2×

Product 1

HCID 86704645(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-bromo-6-(1H-pyrazol-1-yl)pyridin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-oneYield 82.7%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
180 °C

Procedure

To (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 32, 198 mg, 0.382 mmol) was added pyrazole (450 mg, 6.61 mmol) and p-toluenesulfonic acid (20 mg, 0.116 mmol). The mixture was heated by microwave irradiation to 180° C. for 30 minutes. The reaction was diluted with ethyl acetate and aqueous sodium hydroxide (1M). The organic was washed with water and brine and was dried over sodium sulfate, filtered and concentrated. The resultant residue was purified by column chromatography to yield (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-bromo-6-(1H-pyrazol-1-yl)pyridin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (173 mg, 0.316 mmol). LCMS calc.=549.0/551.0. found=549.0/551.0.

Workup

  1. washThe organic was washed with water and brine
  2. dry with materialwas dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resultant residue was purified by column chromatography

Sources & evidence

ORD record
ord-1ba9a094d08b472e9b24ac640a3054bd
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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