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

Reaktionsgleichung

Reaktionsgleichung von HRID 549405
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

Komponenten

7

Edukt 3

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

Produkt 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 esterAusbeute 97,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 44558591Tri-t-butylphosphine fluoroborateKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
135 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-480eefb903c84f53899ee8b0122ec693
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07943652B2

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