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

HRID 909628Notes

Reaction equation

HRID 909628 reaction equation
[CH3:1][C@@H:2]1[C@H:6]([CH3:7])[O:5][C:4]([C:8]2[NH:12][C:11]([C:13]3[CH:14]=[C:15]([OH:25])[CH:16]=[C:17]([O:19][C@@H:20]([CH3:24])[CH2:21][O:22][CH3:23])[CH:18]=3)=[CH:10][CH:9]=2)=[N:3]1.Cl[C:27]1[CH:32]=[N:31][C:30]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:29][N:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>C(#N)C>[CH3:1][C@@H:2]1[C@H:6]([CH3:7])[O:5][C:4]([C:8]2[NH:12][C:11]([C:13]3[CH:14]=[C:15]([CH:16]=[C:17]([O:19][C@@H:20]([CH3:24])[CH2:21][O:22][CH3:23])[CH:18]=3)[O:25][C:27]3[CH:32]=[N:31][C:30]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:29][N:28]=3)=[CH:10][CH:9]=2)=[N:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 666928643-{5-[(4R,5S)-4,5-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl]-5-{[(2S)-1-methoxypropan-2-yl]oxy}phenolHCID 866495742-Chloro-5-(methylsulfonyl)pyrazine

Product 1

HCID 668909802-(3-{5-[(4R,5S)-4,5-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-{[(2S)-1-methoxypropan-2-yl]oxy}phenoxy)-5-(methylsulfonyl)pyrazineYield 84%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

3-{5-[(4R,5S)-4,5-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-{[(2S)-1-methoxypropan-2-yl]oxy}phenol (420 mg, 1.22 mmol) synthesized in Example (109c) was dissolved in acetonitrile (20 mL), and 2-chloro-5-(methylsulfonyl)pyrazine (345 mg, 1.46 mmol) synthesized in Example (97c) and cesium carbonate (1.02 g, 3.13 mmol) were added at room temperature, followed by stirring at room temperature overnight under nitrogen atmosphere. To this reaction solution, water (30 mL) was added, and extraction was carried out with methylene chloride (40 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: methanol/methylene chloride=2%-3%) to afford the desired compound (513 mg, yield 84%) 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: methanol/methylene chloride=2%-3%)

Sources & evidence

ORD record
ord-eb912c36f604409daf0c856abe0bcd4c
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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