Water → (2S)-2-(3-{5-[(5S)-5-Methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenoxy}phenoxy)propan-1-ol

HRID 1964705Notes

Reaction equation

HRID 1964705 reaction equation
[OH:1][CH2:2][C@H:3]([CH3:23])[O:4][C:5]1[CH:6]=[C:7]([OH:22])[CH:8]=[C:9]([C:11]2[NH:12][C:13]([C:16]3[O:17][C@@H:18]([CH3:21])[CH2:19][N:20]=3)=[CH:14][CH:15]=2)[CH:10]=1.F[C:25]1[CH:30]=[CH:29][C:28]([S:31]([N:34]2[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]2)(=[O:33])=[O:32])=[CH:27][CH:26]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH3:21][C@@H:18]1[O:17][C:16]([C:13]2[NH:12][C:11]([C:9]3[CH:10]=[C:5]([CH:6]=[C:7]([O:22][C:25]4[CH:30]=[CH:29][C:28]([S:31]([N:34]5[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]5)(=[O:32])=[O:33])=[CH:27][CH:26]=4)[CH:8]=3)[O:4][C@@H:3]([CH3:23])[CH2:2][OH:1])=[CH:15][CH:14]=2)=[N:20][CH2:19]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 7679141-((4-Fluorophenyl)sulfonyl)-4-methylpiperazineHCID 666809363-[(1S)-2-Hydroxy-1-methylethoxy]-5-{5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenol

Product 1

HCID 58065523(2S)-2-(3-{5-[(5S)-5-Methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}-5-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenoxy}phenoxy)propan-1-olYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

3-[(1S)-2-Hydroxy-1-methylethoxy]-5-{5-[(5S)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]-1H-pyrrol-2-yl}phenol (40 mg, 0.13 mmol) synthesized in Example (117a) and 1-[(4-fluorophenyl)sulfonyl]-4-methylpiperazine (49 mg, 0.19 mmol) synthesized in Example (116a) were dissolved in N,N-dimethylformamide (2 mL), and potassium carbonate (52 mg, 0.38 mmol) was added, followed by stirring at 100° C. for 4 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water (10 mL) was added, and extraction was carried out twice with ethyl acetate (10 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=0%-5%) to afford the desired compound (17 mg, yield 25%) 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=0%-5%)

Sources & evidence

ORD record
ord-e72c65a631f6405baa9b5ac4859b5d3d
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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