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

HRID 1964682
Notes
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Reaction equation

HRID 1964682 reaction equation
[CH2:1]([C@@H:3]1[CH2:7][O:6][C:5]([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:4]1)[CH3:2].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>[CH2:1]([C@@H:3]1[CH2:7][O:6][C:5]([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:4]1)[CH3:2]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 668912093-{5-[(4R)-4-Ethyl-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 668910952-(3-{5-[(4R)-4-Ethyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-{[(2S)-1-methoxypropan-2-yl]oxy}phenoxy)-5-(methylsulfonyl)pyrazine
Yield 105.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

3-{5-[(4R)-4-Ethyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-{[(2S)-1-methoxypropan-2-yl]oxy}phenol (272 mg, 0.79 mmol) synthesized in Example (108b) was dissolved in acetonitrile (5.0 mL), and 2-chloro-5-(methylsulfonyl)pyrazine (220 mg, 1.14 mmol) synthesized in Example (97c) and cesium carbonate (640 mg, 1.96 mmol) were added at room temperature, followed by stirring at room temperature for 3.5 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: methanol/methylene chloride=2%-3%) to afford the desired compound (417 mg, yield ˜100%) as a pale yellow 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-b80c09665a314a4fa60e40546f29060c
Source dataset
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08415359B2

Reaction notes

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