3,5-Dimethyl-4-hydroxybenzonitrile → 4-{2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopropyl-ethoxy}-3,5-dimethyl-benzonitrile

HRID 417155Notes

Reaction equation

HRID 417155 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:16]3[CH2:18][CH2:17]3)[CH2:14][OH:15])[C:11]3[CH:19]=[C:20]([F:24])[C:21]([F:23])=[CH:22][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[CH3:25][C:26]1[CH:27]=[C:28]([CH:31]=[C:32]([CH3:35])[C:33]=1O)[C:29]#[N:30]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:16]3[CH2:18][CH2:17]3)[CH2:14][O:15][C:33]3[C:32]([CH3:35])=[CH:31][C:28]([C:29]#[N:30])=[CH:27][C:26]=3[CH3:25])[C:11]3[CH:19]=[C:20]([F:24])[C:21]([F:23])=[CH:22][C:10]=3[N:9]=2)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 201763,5-Dimethyl-4-hydroxybenzonitrileHCID 666194522-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopropyl-ethanol

Product 1

HCID 666192504-{2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopropyl-ethoxy}-3,5-dimethyl-benzonitrile

Procedure

The title compound was prepared from 2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopropyl-ethanol, 3,5-dimethyl-4-hydroxybenzonitrile (commercially available), tri-n-butylposphine and N′N′N′N-tetramethylazodicarboxamide. The compound was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane:ethyl acetate (100:0 to 60:40). The so-obtained solid was again chromatographed on a preparative HPLC system using a Phenomenex Gemini column eluting with a gradient of acetonitril and water (containing 5% formic acid). White foam (20%). MS (Turbo Spray): m/z=478.149 [M+H].

Workup

  1. customThe compound was purified by silica gel chromatography
  2. washeluting with a gradient of heptane:ethyl acetate (100:0 to 60:40)
  3. customThe so-obtained solid was again chromatographed on a preparative HPLC system
  4. washeluting with a gradient of acetonitril and water (containing 5% formic acid)

Sources & evidence

ORD record
ord-92796aaced8244e7a84225b736b03c90
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

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