Water → 2-(Azetidin-1-ylsulfonyl)-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenoxy)-pyridine

HRID 909654Notes

Reaction equation

HRID 909654 reaction equation
[N:1]1([S:5]([C:8]2[CH:13]=[CH:12][C:11](Cl)=[CH:10][N:9]=2)(=[O:7])=[O:6])[CH2:4][CH2:3][CH2:2]1.[CH3:15][O:16][CH2:17][C@H:18]([CH3:38])[O:19][C:20]1[CH:21]=[C:22]([OH:37])[CH:23]=[C:24]([C:26]2[NH:27][C:28]([C:31]3[O:32][C@@H:33]([CH3:36])[CH2:34][N:35]=3)=[CH:29][CH:30]=2)[CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O>[N:1]1([S:5]([C:8]2[CH:13]=[CH:12][C:11]([O:37][C:22]3[CH:23]=[C:24]([C:26]4[NH:27][C:28]([C:31]5[O:32][C@@H:33]([CH3:36])[CH2:34][N:35]=5)=[CH:29][CH:30]=4)[CH:25]=[C:20]([O:19][C@@H:18]([CH3:38])[CH2:17][O:16][CH3:15])[CH:21]=3)=[CH:10][N:9]=2)(=[O:7])=[O:6])[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 666811783-[(1S)-2-Methoxy-1-methylethoxy]-5-{5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenolHCID 666833922-(Azetidin-1-ylsulfonyl)-5-chloropyridine

Product 1

HCID 580655192-(Azetidin-1-ylsulfonyl)-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenoxy)-pyridineYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

2-(Azetidin-1-ylsulfonyl)-5-chloropyridine (170 mg, 0.73 mmol) synthesized in Example (119b) and 3-[(1S)-2-methoxy-1-methylethoxy]-5-{5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenol (230 mg, 0.70 mmol) synthesized in Example (116d) were dissolved in N,N-dimethylformamide (3.5 mL), and cesium carbonate (454 mg, 1.39 mmol) was added, followed by stirring at 100° C. for 2 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water (20 mL) was added, and extraction was carried out twice with ethyl acetate (20 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=5%-50%) to afford the desired compound (273 mg, yield 75%) as a white solid.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionextraction
  3. washThe organic layer was washed with saturated brine
  4. dry with materialsubsequently dried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe resulting residue was purified
  7. washsilica gel column chromatography (elution solvent: methanol/methylene chloride=5%-50%)

Sources & evidence

ORD record
ord-0105b2b5dc214c58b1cddeaf4874787c
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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