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

反応式

HRID 549405 の反応式
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

参加物

7

反応物 3

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

生成物 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 ester収率 97.1%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 44558591Tri-t-butylphosphine fluoroborate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
135 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-480eefb903c84f53899ee8b0122ec693
出典データセット
uspto-grants-2011_05
特許番号
US07943652B2

関連ノート

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