Cesium carbonate → 5-bromo-1-methyl-3-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)pyridin-2(1H)-one

HRID 68441ノート

反応式

HRID 68441 の反応式
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]([NH2:14])=[N:12][CH:13]=2)[CH2:4][CH2:3]1.Br[C:16]1[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=[C:20]([Br:22])[CH:21]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[Br:22][C:20]1[CH:21]=[C:16]([NH:14][C:11]2[CH:10]=[CH:9][C:8]([N:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)=[CH:13][N:12]=2)[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=1

参加物

6

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 223298335-(4-Methylpiperazin-1-yl)pyridin-2-amine

生成物 1

HCID 592164475-bromo-1-methyl-3-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)pyridin-2(1H)-one収率 27.8%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

To 5-(4-Methyl-piperazin-1-yl)-pyridin-2-ylamine (1.06 g, 5.53 mmol), 3,5-Dibromo-1-methyl-1H-pyridin-2-one (1.23 g, 4.61 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (400 mg, 0.691 mmol), and cesium carbonate (4.50 g, 13.8 mmol) was added 45 mL 1,4-dioxane and tris(dibenzylidineacetone)dipalladium(0) (422 mg, 0.461 mmol). This was heated in a 120° C. oil bath for 6 hours under argon. This was partitioned between ethylacetate and dilute aqueous sodium bicarbonate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by flash chromatography (gradient elution with 2 to 5% methanol/dichloromethane) to yield 5-Bromo-1-methyl-3-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-1H-pyridin-2-one (484 mg, 1.28 mmol). MS (ESI) 380.0 (M+H)+.

後処理

  1. customThis was partitioned between ethylacetate and dilute aqueous sodium bicarbonate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. custompurified by flash chromatography (gradient elution with 2 to 5% methanol/dichloromethane)

出典と根拠

ORDレコード
ord-6970fe522c37435098525606d0bce66f
出典データセット
uspto-grants-2014_09
特許番号
US08822457B2

反応ノート

読み込み中…