Potassium Hydroxide → HCID 44817939, compound

HRID 885897Notes

Reaction equation

HRID 885897 reaction equation
[OH-].[K+].C([O:7][C:8](=[O:19])/[CH:9]=[CH:10]/[C:11]1[CH:16]=[CH:15][C:14]([CH:17]=O)=[CH:13][N:12]=1)(C)(C)C.[CH3:20][N:21]1[CH2:26][CH2:25][N:24]([CH2:27][C:28]2[CH:29]=[C:30]([C:34](=[O:36])[CH3:35])[CH:31]=[CH:32][CH:33]=2)[CH2:23][CH2:22]1>CCO.O>[CH3:20][N:21]1[CH2:26][CH2:25][N:24]([CH2:27][C:28]2[CH:29]=[C:30]([C:34](=[O:36])/[CH:35]=[CH:17]/[C:14]3[CH:15]=[CH:16][C:11](/[CH:10]=[CH:9]/[C:8]([OH:7])=[O:19])=[N:12][CH:13]=3)[CH:31]=[CH:32][CH:33]=2)[CH2:23][CH2:22]1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 44819897tert-Butyl (E)-3-(5-formyl-pyridin-2-yl)-acrylateHCID 59312567HCID 59312567, compound

Product 1

HCID 44817939HCID 44817939, compoundYield 47.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

1.7 M KOH (0.634 ml) was added dropwise to a stirred mixture of (E)-3-(5-formyl-pyridin-2-yl)-acrylic acid tert-butyl ester (see Example 11 STEP A-D, 250 mg, 1.078 mmol) and 1-[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-ethanone (obtained as described in Preparation 14, 250 mg, 1.078 mmol) in EtOH (15 ml). The resulting solution was stirred at 0° C. for 7 h and then diluted with water and extracted with AcOEt. The organic phase was dried over Na2SO4 and evaporated in vacuo. The crude product was purified by chromatographic column (eluent: DCM/MeOH/NH4OH from 97:3:0.1 to 95:5:0.2) and the desired intermediate was dissolved in DCM (4 ml) and TFA (1 ml). The mixture was stirred at room temperature for 6 h and then the solvent was removed in vacuo to give 200 mg of (E)-3-(5-{(E)-3-[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-oxo-propenyl}-pyridin-2-yl)-acrylic acid as its tris-trifluoroacetate salt. The crude mixture was used in the next step without further purifications.

Workup

  1. extractionextracted with AcOEt
  2. dry with materialThe organic phase was dried over Na2SO4
  3. customevaporated in vacuo
  4. customThe crude product was purified by chromatographic column (eluent: DCM/MeOH/NH4OH from 97:3:0.1 to 95:5:0.2)
  5. dissolutionthe desired intermediate was dissolved in DCM (4 ml)
  6. stirringThe mixture was stirred at room temperature for 6 h
  7. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-da9068403c564f94999e0456cb1181dd
Source dataset
uspto-grants-2012_08
Patent number
US08242175B2

Reaction notes

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