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

HRID 909641Notes

Reaction equation

HRID 909641 reaction equation
[OH:1][C@@H:2]([C@@H:4]1[CH2:8][O:7][C:6]([C:9]2[NH:13][C:12]([C:14]3[CH:15]=[C:16]([OH:26])[CH:17]=[C:18]([O:20][C@@H:21]([CH3:25])[CH2:22][O:23][CH3:24])[CH:19]=3)=[CH:11][CH:10]=2)=[N:5]1)[CH3:3].Cl[C:28]1[CH:33]=[N:32][C:31]([S:34]([CH3:37])(=[O:36])=[O:35])=[CH:30][N:29]=1.C(=O)([O-])[O-].[K+].[K+].O>C(#N)C>[CH3:24][O:23][CH2:22][C@@H:21]([O:20][C:18]1[CH:19]=[C:14]([C:12]2[NH:13][C:9]([C:6]3[O:7][CH2:8][C@@H:4]([C@H:2]([OH:1])[CH3:3])[N:5]=3)=[CH:10][CH:11]=2)[CH:15]=[C:16]([O:26][C:28]2[CH:33]=[N:32][C:31]([S:34]([CH3:37])(=[O:36])=[O:35])=[CH:30][N:29]=2)[CH:17]=1)[CH3:25]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 666818293-(5-{(4S)-4-[(1R)-1-Hydroxyethyl]-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 51041151(1R)-1-{(4S)-2-[5-(3-{[(2S)-1-Methoxypropan-2-yl]oxy}-5-{[5-(methylsulfonyl)pyrazin-2-yl]oxy}phenyl)-1H-pyrrol-2-yl]-4,5-dihydro-1,3-oxazol-4-yl}ethanolYield 81%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

3-(5-{(4S)-4-[(1R)-1-Hydroxyethyl]-4,5-dihydro-1,3-oxazol-2-yl}-1H-pyrrol-2-yl)-5-{[(2S)-1-methoxypropan-2-yl]oxy}phenol (766 mg, 2.13 mmol) synthesized in Example (114c) was dissolved in acetonitrile (15 mL), and 2-chloro-5-(methylsulfonyl)pyrazine (590 mg, 3.06 mmol) synthesized in Example (97c) and potassium carbonate (870 mg, 6.29 mmol) were added, followed by stirring at room temperature for 4 hours under nitrogen atmosphere. Water (50 mL) was added, and extraction was carried out with methylene chloride (50 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/ethyl acetate=5%-8%) to afford the desired compound (890 mg, yield 81%) 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/ethyl acetate=5%-8%)

Sources & evidence

ORD record
ord-05d5e81337ec4b0c94067ac907c567ef
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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