Methyl Acrylate → (E)-3-{4-[4-methyl-1-(2-pyrazolo[1,5-a]pyridin-3-yl-ethyl)-piperazin-2-yl]-phenyl}-acrylic acid methyl ester

HRID 549405

Reaction equation

HRID 549405 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][N:12]([CH3:14])[CH2:11][CH2:10][N:9]2[CH2:15][CH2:16][C:17]2[CH:18]=[N:19][N:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=23)=[CH:4][CH:3]=1.[C:26]([O:30][CH3:31])(=[O:29])[CH:27]=[CH2:28].CN(C1CCCCC1)C1CCCCC1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.F[B-](F)(F)F>[CH3:31][O:30][C:26](=[O:29])/[CH:27]=[CH:28]/[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][N:12]([CH3:14])[CH2:11][CH2:10][N:9]2[CH2:15][CH2:16][C:17]2[CH:18]=[N:19][N:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=23)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 7294Methyl AcrylateHCID 24210N-Methyl dicyclohexylamineHCID 578992473-{2-[2-(4-Bromo-phenyl)-4-methyl-piperazin-1-yl]-ethyl}-pyrazolo[1,5-a]pyridine

Product 1

HCID 57899306(E)-3-{4-[4-methyl-1-(2-pyrazolo[1,5-a]pyridin-3-yl-ethyl)-piperazin-2-yl]-phenyl}-acrylic acid methyl esterYield 97.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 44558591Tri-t-butylphosphine fluoroborateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of 3-{2-[2-(4-bromo-phenyl)-4-methyl-piperazin-1-yl]-ethyl}-pyrazolo[1,5-a]pyridine (1.0 g, 2.49 mmol), methyl acrylate (0.458 mL, 4.98 mmol), N-methyldicyclohexylamine (584 mg, 2.99 mmol), tri-(tert-butyl)phosphine-tetrafluoroborate (28.9 mg, 0.0997 mmol) and Pd2(dba)3 (22.8 mg, 0.02 mmol) in 1,4-dioxane (10 mL) was flushed with nitrogen and heated at 100° C. for 1 h and at 135° C. for 1 h under microwave irradiation. The reaction mixture was cooled to room temperature, filtered through Celite pad, and concentrated in vacuo. Purification via flash silica gel column chromatography (heptane/ethyl acetate) gave (E)-3-{4-[4-methyl-1-(2-pyrazolo[1,5-a]pyridin-3-yl-ethyl)-piperazin-2-yl]-phenyl}-acrylic acid methyl ester (0.978 g, 97% yield). LCMS (m/z): 405.30 (M+1).

Workup

  1. customwas flushed with nitrogen
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered through Celite pad
  4. concentrationconcentrated in vacuo
  5. customPurification via flash silica gel column chromatography (heptane/ethyl acetate)

Sources & evidence

ORD record
ord-480eefb903c84f53899ee8b0122ec693
Source dataset
uspto-grants-2011_05
Patent number
US07943652B2

Linked notes

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