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

HRID 417150Notes

Reaction equation

HRID 417150 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:14][OH:15])[C:11]3[CH:21]=[C:22]([F:26])[C:23]([F:25])=[CH:24][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[CH3:27][C:28]1[CH:29]=[C:30]([CH:33]=[C:34]([CH3:37])[C:35]=1O)[C:31]#[N:32]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:16]3[CH2:17][CH2:18][CH2:19][CH2:20]3)[CH2:14][O:15][C:35]3[C:34]([CH3:37])=[CH:33][C:30]([C:31]#[N:32])=[CH:29][C:28]=3[CH3:27])[C:11]3[CH:21]=[C:22]([F:26])[C:23]([F:25])=[CH:24][C:10]=3[N:9]=2)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 201763,5-Dimethyl-4-hydroxybenzonitrileHCID 666194742-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopentyl-ethanol

Product 1

HCID 666193814-{2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopentyl-ethoxy}-3,5-dimethyl-benzonitrile

Procedure

The title compound was prepared in analogy to Example 4, intermediate, from 2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopentyl-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 n-heptane:ethyl acetate (100:0 to 60:40). The product containing fractions were pooled and evaporated. The resulting light yellow foam was dissolved in acetonitrile, upon which crystallisation occurred. The suspension was filtered, washed with a small amount of acetonitrile and dried under high vacuum. White solid (34%). MS (Turbo Spray): m/z=506.182 [M+H].

Workup

  1. customThe compound was purified by silica gel chromatography
  2. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 60:40)
  3. additionThe product containing fractions
  4. customevaporated
  5. dissolutionThe resulting light yellow foam was dissolved in acetonitrile, upon which crystallisation
  6. filtrationThe suspension was filtered
  7. washwashed with a small amount of acetonitrile
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-2973b330bd6344cf825938ff589a7bbb
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

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