Potassium Hydroxide → (E)-3-(5-{(E)-3-[2-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-oxo-propenyl}-pyridin-2-yl)-acrylic acid

HRID 885889Notes

Reaction equation

HRID 885889 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15](=[O:17])[CH3:16])[CH2:4][CH2:3]1.C([O:22][C:23](=[O:34])/[CH:24]=[CH:25]/[C:26]1[CH:31]=[CH:30][C:29]([CH:32]=O)=[CH:28][N:27]=1)(C)(C)C.[OH-].[K+]>CCO.O>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15](=[O:17])/[CH:16]=[CH:32]/[C:29]2[CH:30]=[CH:31][C:26](/[CH:25]=[CH:24]/[C:23]([OH:34])=[O:22])=[N:27][CH:28]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 44819897tert-Butyl (E)-3-(5-formyl-pyridin-2-yl)-acrylateHCID 593125691-[2-(4-Methyl-piperazin-1-yl-methyl)phenyl]-ethanone

Product 1

HCID 44817767(E)-3-(5-{(E)-3-[2-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-oxo-propenyl}-pyridin-2-yl)-acrylic acidYield 133.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
4 °C

Procedure

A mixture of 1-[2-(4-methyl-piperazin-1-ylmethyl)-phenyl]-ethanone (obtained as described in Preparation 11, 250 mg, 1.07 mmol), (E)-3-(5-formyl-pyridin-2-yl)-acrylic acid tert-butyl ester (described in Example 11 STEP A-D, 251 mg, 1.07 mmol) and 1.7 M KOH (0.633 ml) in EtOH (10 ml) was stirred at 4° C. overnight. The resulting solution was diluted with water and extracted with AcOEt. The organic phase was dried over Na2SO4 and evaporated in vacuo. The crude reaction mixture was purified by column chromatography (eluent: DCM/MeOH/NH4OH 95:5:0.2) and the resulting product was dissolved in DCM (10 ml) and TFA (2 ml) and stirred at room temperature for 4 h. The solvent was evaporated to give 558 mg of (E)-3-(5-{(E)-3-[2-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-oxo-propenyl}-pyridin-2-yl)-acrylic acid as its tris-trifluoroacetate salt.

Workup

  1. extractionextracted with AcOEt
  2. dry with materialThe organic phase was dried over Na2SO4
  3. customevaporated in vacuo
  4. customThe crude reaction mixture
  5. customwas purified by column chromatography (eluent: DCM/MeOH/NH4OH 95:5:0.2)
  6. dissolutionthe resulting product was dissolved in DCM (10 ml)
  7. stirringTFA (2 ml) and stirred at room temperature for 4 h
  8. customThe solvent was evaporated

Sources & evidence

ORD record
ord-e9f018ffffd54a8fa865c2b80193621f
Source dataset
uspto-grants-2012_08
Patent number
US08242175B2

Reaction notes

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