Pyrazole → 3-(1-{[2-(1H-pyrazol-1-yl)-3',5'-bis(trifluoromethyl)biphenyl-4-yl]carbonyl}pyrrolidin-3-yl)pyridine

HRID 383781

Reaction equation

HRID 383781 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([N:10]2[CH2:14][CH2:13][CH:12]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)[CH2:11]2)=[O:9])[CH:5]=[CH:4][C:3]=1[C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=1.[NH:35]1[CH:39]=[CH:38][CH:37]=[N:36]1.C(=NO)C1C(=CC=CC=1)O.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C.[Cu-]=O>[N:35]1([C:2]2[CH:7]=[C:6]([C:8]([N:10]3[CH2:14][CH2:13][CH:12]([C:15]4[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=4)[CH2:11]3)=[O:9])[CH:5]=[CH:4][C:3]=2[C:21]2[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=2)[CH:39]=[CH:38][CH:37]=[N:36]1

Participants

7

Reactant 4

HCID 1048PyrazoleHCID 7200Salicylaldehyde oximeHCID 10796Cesium carbonateHCID 866577533-(1-{[2-Bromo-3',5'-bis(trifluoromethyl)biphenyl-4-yl]carbonyl}pyrrolidin-3-yl)pyridine

Product 1

HCID 468475913-(1-{[2-(1H-pyrazol-1-yl)-3',5'-bis(trifluoromethyl)biphenyl-4-yl]carbonyl}pyrrolidin-3-yl)pyridine

Reagents, catalysts & solvents 2

HCID 178419072HCID 178419072, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of 3b (54.0 mg, 0.099 mmol), pyrazole (50.7 mg, 0.745 mmol), salicylaldoxime (19.8 mg, 0.145 mmol), copper(I) oxide (16.6 mg, 0.116 mmol) and cesium carbonate (265 mg, 0.812 mmol) in acetonitrile (1.00 mL) was heated to 120° C. in a sealed microwave vial for a total of 60 min. The reaction mixture was cooled to rt, concentrated in vacuo, and the resulting crude residue was purified by preparative reversed phase HPLC on YMC Pack Pro C18 stationary phase (CH3CN/H2O as eluent, 0.05% TFA as modifier), followed by lyophilization of the purified fractions to afford the title compound 10a. m/z (ES) 531 (MH)+.

Workup

  1. concentrationconcentrated in vacuo
  2. customthe resulting crude residue was purified by preparative reversed phase HPLC on YMC Pack Pro C18 stationary phase (CH3CN/H2O as eluent, 0.05% TFA as modifier)

Sources & evidence

ORD record
ord-a453bc123ad646129051bb5ef7295e14
Source dataset
uspto-grants-2013_02
Patent number
US08367679B2

Linked notes

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