Trifluoroacetic acid → 3-(3-(1-benzyl-1H-pyrazol-4-yl)pyridin-2-yloxy)-N-(3-isopropylphenyl)-4-methylbenzamide

HRID 883027Notes

Reaction equation

HRID 883027 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[CH3:20])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]([CH3:16])[CH3:15])[CH:9]=1)=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:27]([N:34]1[CH:38]=[C:37]([C:39]2[C:40](Cl)=[N:41][CH:42]=[CH:43][CH:44]=2)[CH:36]=[N:35]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(O)(C(F)(F)F)=O>CCOC(C)=O.O>[CH2:27]([N:34]1[CH:38]=[C:37]([C:39]2[C:40]([O:1][C:2]3[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=3[CH3:20])[C:5]([NH:7][C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]([CH3:16])[CH3:15])[CH:9]=3)=[O:6])=[N:41][CH:42]=[CH:43][CH:44]=2)[CH:36]=[N:35]1)[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 288804893-hydroxy-N-(3-isopropylphenyl)-4-methylbenzamideHCID 866237863-(1-benzyl-1H-pyrazol-4-yl)-2-chloropyridine

Product 1

HCID 251022303-(3-(1-benzyl-1H-pyrazol-4-yl)pyridin-2-yloxy)-N-(3-isopropylphenyl)-4-methylbenzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

3-Hydroxy-N-(3-isopropylphenyl)-4-methylbenzamide (100 mg, 0.371 mmol), cesium carbonate (220 mg, 0.676 mmol) and 3-(1-benzyl-1H-pyrazol-4-yl)-2-chloropyridine (91.0 mg, 0.338 mmol) were combined in an argon-purged sealed tube. DMSO (1.5 mL) was added and the mixture was heated to 130° C. for 23 hours. The cooled reaction was diluted with EtOAc and water and then neutralized with TFA (pH˜7). The separated organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified first by silica gel chromatography (1:1 MTBE/benzene) followed by trituration of the resulting solid with 20:1 hexanes/EtOAc to yield 3-(3-(1-benzyl-1H-pyrazol-4-yl)pyridin-2-yloxy)-N-(3-isopropylphenyl)-4-methylbenzamide as an off-white solid. MS m/z=503 [M+1]+. Calc'd for C32H30N4O2: 502.62.

Workup

  1. custompurged
  2. customsealed tube
  3. additionDMSO (1.5 mL) was added
  4. customThe cooled reaction
  5. dry with materialThe separated organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified first by silica gel chromatography (1:1 MTBE/benzene)

Sources & evidence

ORD record
ord-62b4752bf96b4874951a3ddd7db92e57
Source dataset
uspto-grants-2012_08
Patent number
US08236823B2

Reaction notes

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