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

HRID 885892Notes

Reaction equation

HRID 885892 reaction equation
[C:1]([C:4]1[CH:19]=[CH:18][C:7]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([C:15](=[O:17])[CH3:16])[CH2:11][CH2:10]2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].C([O:24][C:25](=[O:36])/[CH:26]=[CH:27]/[C:28]1[CH:33]=[CH:32][C:31]([CH:34]=O)=[CH:30][N:29]=1)(C)(C)C.[OH-].[K+]>CCO>[C:15]([N:12]1[CH2:13][CH2:14][N:9]([CH2:8][C:7]2[CH:18]=[CH:19][C:4]([C:1](=[O:3])/[CH:2]=[CH:34]/[C:31]3[CH:32]=[CH:33][C:28](/[CH:27]=[CH:26]/[C:25]([OH:36])=[O:24])=[N:29][CH:30]=3)=[CH:5][CH:6]=2)[CH2:10][CH2:11]1)(=[O:17])[CH3:16]

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 44819897tert-Butyl (E)-3-(5-formyl-pyridin-2-yl)-acrylateHCID 596069451-[4-(4-Acetyl-benzyl)piperazin-1-yl]-ethanone

Product 1

HCID 67049888(E)-3-(5-{(E)-3-[4-(4-acetyl-piperazin-1-ylmethyl)-phenyl]-3-oxo-propenyl}-pyridin-2-yl)-acrylic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1-[4-(4-acetyl-benzyl)piperazin-1-yl]-ethanone (prepared following the procedure described in Preparation 12, 500 mg, 1.92 mmol), (E)-3-(5-formyl-pyridin-2-yl)-acrylic acid tert-butyl ester (described in Example 11 STEP A-D, 448 mg, 1.92 mmol) and 1.7 M KOH (1.2 ml) in EtOH (19 ml) was stirred at room temperature for 6 h and then partitioned between water and 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 97:3:0.1) and the resulting product was dissolved in DCM (1.5 ml) and TFA (0.560 ml). The solution was stirred at room temperature for 3 h and then the solvent was evaporated to give 300 mg (E)-3-(5-{(E)-3-[4-(4-acetyl-piperazin-1-ylmethyl)-phenyl]-3-oxo-propenyl}-pyridin-2-yl)-acrylic acid as its bis-trifluoroacetate salt (the compound was used without further purification in the next step).

Workup

  1. customprepared
  2. custompartitioned between water and AcOEt
  3. dry with materialThe organic phase was dried over Na2SO4
  4. customevaporated in vacuo
  5. customThe crude reaction mixture
  6. customwas purified by column chromatography (eluent: DCM/MeOH/NH4OH 97:3:0.1)
  7. dissolutionthe resulting product was dissolved in DCM (1.5 ml)
  8. stirringThe solution was stirred at room temperature for 3 h
  9. customthe solvent was evaporated

Sources & evidence

ORD record
ord-19dec6cc87e94716a75417fb043553fd
Source dataset
uspto-grants-2012_08
Patent number
US08242175B2

Reaction notes

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