Water → 2-(3-{[(2S)-1-Methoxypropan-2-yl]oxy}-5-{5-[(4R)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenoxy)-5-(methylsulfonyl)pyrazine

HRID 1964679Notes

Reaction equation

HRID 1964679 reaction equation
[CH3:1][O:2][CH2:3][C@@H:4]([O:6][C:7]1[CH:8]=[C:9]([OH:24])[CH:10]=[C:11]([C:13]2[NH:14][C:15]([C:18]3[O:19][CH2:20][C@@H:21]([CH3:23])[N:22]=3)=[CH:16][CH:17]=2)[CH:12]=1)[CH3:5].Br[C:26]1[CH:31]=[N:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][N:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>C(#N)C>[CH3:1][O:2][CH2:3][C@@H:4]([O:6][C:7]1[CH:8]=[C:9]([CH:10]=[C:11]([C:13]2[NH:14][C:15]([C:18]3[O:19][CH2:20][C@@H:21]([CH3:23])[N:22]=3)=[CH:16][CH:17]=2)[CH:12]=1)[O:24][C:26]1[CH:31]=[N:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][N:27]=1)[CH3:5]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 666831893-{[(2S)-1-Methoxypropan-2-yl]oxy}-5-{5-[(4R)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenolHCID 722192792-Bromo-5-(methylsulfonyl)pyrazine

Product 1

HCID 666826612-(3-{[(2S)-1-Methoxypropan-2-yl]oxy}-5-{5-[(4R)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenoxy)-5-(methylsulfonyl)pyrazineYield 91%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

3-{[(2S)-1-Methoxypropan-2-yl]oxy}-5-{5-[(4R)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenol (340 mg, 1.03 mmol) synthesized in Example (107c) was dissolved in acetonitrile (10 mL), and 2-bromo-5-(methylsulfonyl)pyrazine (300 mg, 1.27 mmol) synthesized in Example (107d) and cesium carbonate (850 mg, 2.61 mmol) were added at room temperature, followed by stirring at room temperature for 4.5 hours under nitrogen atmosphere. To this reaction solution, water (20 mL) was added, and extraction was carried out with methylene chloride (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=100%) to afford the desired compound (456 mg, yield 91%) as a white solid.

Workup

  1. extractionextraction
  2. washThe organic layer was washed with saturated brine
  3. dry with materialsubsequently dried over anhydrous magnesium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe resulting residue was purified
  6. washsilica gel column chromatography (elution solvent: ethyl acetate=100%)

Sources & evidence

ORD record
ord-5c9498b4939e4fb5aee0af8debfb95d0
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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