Acrylic Acid → 3-[3-(1H-benzoimidazol-2-yl)-phenyl]-N-(tetrahydro-pyran-2-yloxy)-acrylamide

HRID 1375689Notes

Reaction equation

HRID 1375689 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][CH:13]=1)[CH:6]=[CH:7][C:8]([OH:10])=O)=O.C(O)(=O)C=C.[CH:19]1[CH:20]=[CH:21][C:22]2[N:27](O)N=[N:25][C:23]=2[CH:24]=1.CCN=C=NCCCN(C)C.[O:40]1[CH2:45][CH2:44][CH2:43][CH2:42][CH:41]1[O:46][NH2:47].CCN(C(C)C)C(C)C>CCO.CN(C=O)C.O>[NH:27]1[C:22]2[CH:21]=[CH:20][CH:19]=[CH:24][C:23]=2[N:25]=[C:1]1[C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][C:8]([NH:47][O:46][CH:41]2[CH2:42][CH2:43][CH2:44][CH2:45][O:40]2)=[O:10])[CH:11]=[CH:12][CH:13]=1

Participants

10

Reactant 6

HCID 6581Acrylic AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 542035293-Formylcinnamic acid

Product 1

HCID 724240283-[3-(1H-benzoimidazol-2-yl)-phenyl]-N-(tetrahydro-pyran-2-yloxy)-acrylamide

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of the appropriate 3-formyl-cinnamic acid (3, 0.57 mmol) and the appropriate substituted-phenyl-1,2-diamine (0.57 mmol) in EtOH (5.0 mL) was refluxed for 24 hrs. The reaction was cooled, evaporated to dryness, and the resulting acrylic acid was used without further purification. To a solution of the acrylic acid (0.25 mmol) and HOBt (0.38 mmol) in DMF (5.0 mL) was added EDCI (0.38 mmol), O-(tetrahydro-pyran-2-yl)-hydroxylamine (0.38 mmol), and DIEA (0.75 mmol). The reaction was stirred at ambient temperature for 18 hrs. The resulting mixture was poured into H2O, extracted with EtOAc, washed with brine, dried over MgSO4 and concentrated to dryness. The resulting material was purified via flash chromatography to yield the desired 3-[3-(1H-benzoimidazol-2-yl)-phenyl]-N-(tetrahydro-pyran-2-yloxy)-acrylamide (11).

Workup

  1. temperatureThe reaction was cooled
  2. customevaporated to dryness
  3. customthe resulting acrylic acid was used without further purification
  4. extractionextracted with EtOAc
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated to dryness
  8. customThe resulting material was purified via flash chromatography

Sources & evidence

ORD record
ord-8cde58567e614073b8279e1218da31a8
Source dataset
uspto-grants-2007_01
Patent number
US07169801B2

Reaction notes

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