Methanol → 2-(2-(4-Bromo-2-fluorophenyl)-4-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-1H-imidazol-1-yl)ethanol

HRID 2044267Notes

Reaction equation

HRID 2044267 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][CH:10]=[C:11]([C:13]3[N:17]([CH:18]([CH3:20])[CH3:19])[N:16]=[C:15]([CH3:21])[N:14]=3)[N:12]=2)=[C:4]([F:22])[CH:3]=1.C1(=O)O[CH2:26][CH2:25][O:24]1.CO>C1(C)C=CC=CC=1.C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH2:26][CH2:25][OH:24])[CH:10]=[C:11]([C:13]3[N:17]([CH:18]([CH3:19])[CH3:20])[N:16]=[C:15]([CH3:21])[N:14]=3)[N:12]=2)=[C:4]([F:22])[CH:3]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 7303Ethylene carbonateHCID 178432629HCID 178432629, compound

Product 1

HCID 582044142-(2-(4-Bromo-2-fluorophenyl)-4-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-1H-imidazol-1-yl)ethanolYield 71%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent3×

Procedure

A suspension of 5-[2-(4-bromo-2-fluoro-phenyl)-1H-imidazol-4-yl]-1-isopropyl-3-methyl-1H-[1,2,4]triazole (2.9 g, 7.96 mmol) in toluene (50 mL) was treated with ethylene carbonate (25 mL) and heated at reflux for 5 h. The cooled reaction mixture was diluted with DCM and passed through a pad of silica eluting with DCM then 20% methanol in DCM. Methanolic fractions were combined and concentrated in vacuo to give a pale tan solid. The solid was triturated in diethyl ether to give 2-[2-(4-Bromo-2-fluoro-phenyl)-4-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-imidazol-1-yl]-ethanol as a white solid (2.3 g, 71%). LCMS: RT=2.85 min, [M+H]+=408/410. 1H NMR 400 MHz (CDCl3) δ: 8.16 (1H, s), 7.67-7.20 (3H, m), 5.83 (1H, m), 4.05 (2H, t, J=5.10 Hz), 3.92 (2H, t, J=5.10 Hz), 2.44 (3H, s), 1.50 (6H, d, J=6.65 Hz).

Workup

  1. temperatureheated
  2. temperatureat reflux for 5 h
  3. customThe cooled reaction mixture
  4. concentrationconcentrated in vacuo
  5. customto give a pale tan solid
  6. customThe solid was triturated in diethyl ether

Sources & evidence

ORD record
ord-615e745da4904bde9a72c9ce0d8403b3
Source dataset
uspto-grants-2013_11
Patent number
US08586574B2

Reaction notes

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