Pyridine → (4-(5-(2'-Methyl-2-(trifluoromethyl)biphenyl-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)methanol

HRID 2404361Notes

Reaction equation

HRID 2404361 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14](O)=[O:15])=[CH:10][C:9]=1[C:17]([F:20])([F:19])[F:18].O[N:22]=[C:23]([C:25]1[CH:30]=[CH:29][C:28]([CH2:31][OH:32])=[CH:27][CH:26]=1)[NH2:24].N1C=CC=CC=1>CC#N>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[O:15][N:24]=[C:23]([C:25]3[CH:30]=[CH:29][C:28]([CH2:31][OH:32])=[CH:27][CH:26]=3)[N:22]=2)=[CH:10][C:9]=1[C:17]([F:19])([F:20])[F:18]

Participants

5

Reactant 3

HCID 1049PyridineHCID 53437716N-Hydroxy-4-(hydroxymethyl)benzimidamideHCID 594958132'-Methyl-2-(trifluoromethyl)-[1,1'-biphenyl]-4-carboxylic acid

Product 1

HCID 66652884(4-(5-(2'-Methyl-2-(trifluoromethyl)biphenyl-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)methanol

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of Intermediate 5 (4.32 g, 15.4 mmol) in MeCN (15 mL) was added 1-ethyl-3-dimethyl aminopropylcarbodiimide (4.14 g, 21.6 mmol) followed by Intermediate 72 (2.81 g, 17.0 mmol). The mixture was stirred at RT for 18 hours and then pyridine (5 mL) added. The mixture was heated under microwave irradiation at 150° C. for 30 minutes. The solvent was removed in vacuo and the residue partitioned between DCM and H2O. The layers were separated, the organic layer washed with H2O and the mixture passed through a hydrophobic frit. The solvent was removed in vacuo and the residue was recrystallised from EtOAc and petrol to give the title compound as a white solid. 1H NMR (CDCl3, 400 MHz) δ 8.63 (1H, s), 8.40 (1H, d, J=8.0 Hz), 8.20 (2H, d, J=8.0 Hz), 7.54 (2H, d, J=7.9 Hz), 7.47 (1H, d, J=7.9 Hz), 7.38-7.21 (3H, m), 7.16 (1H, d, J=7.5 Hz), 4.81 (2H, d, J=5.7 Hz), 2.14-1.94 (3H, m). LC/MS (Method A): 411 (M+H)+. HPLC (Method G) Rt 4.50 min (Purity: 97.9%).

Workup

  1. temperatureThe mixture was heated under microwave irradiation at 150° C. for 30 minutes
  2. customThe solvent was removed in vacuo
  3. customthe residue partitioned between DCM and H2O
  4. customThe layers were separated
  5. washthe organic layer washed with H2O
  6. customThe solvent was removed in vacuo
  7. customthe residue was recrystallised from EtOAc and petrol

Sources & evidence

ORD record
ord-4aba0769058b4e2291111974166e243d
Source dataset
uspto-grants-2014_08
Patent number
US08802704B2

Reaction notes

Loading…