Dimethyl Sulfoxide → 3,3-dimethyl-1-(1-(5-methylpyridin-2-yl)piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one

HRID 707335ノート

反応式

HRID 707335 の反応式
Cl.Cl.[CH3:3][C:4]1([CH3:20])[C:12]2[C:7](=[N:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[C:5]1=[O:19].C([O-])(=O)C.[Cs+].Br[C:27]1[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][N:28]=1.CS(C)=O>C(OCC)(=O)C.[OH-].[NH4+].[Cu]>[CH3:3][C:4]1([CH3:20])[C:12]2[C:7](=[N:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH:13]2[CH2:18][CH2:17][N:16]([C:27]3[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][N:28]=3)[CH2:15][CH2:14]2)[C:5]1=[O:19]

参加物

8

反応物 4

HCID 679Dimethyl SulfoxideHCID 5642162-Bromo-5-methylpyridine2 回HCID 5152919Cesium acetateHCID 866941923,3-dimethyl-1-(piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one dihydrochloride2 回

生成物 1

HCID 866941943,3-dimethyl-1-(1-(5-methylpyridin-2-yl)piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one収率 24.7%

試薬・触媒・溶媒 3

HCID 23978Copper触媒HCID 8857Ethyl Acetate溶媒HCID 14923Ammonium Hydroxide溶媒

反応条件

温度
100 °C

実験手順

A mixture of 3,3-dimethyl-1-(piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one dihydrochloride (intermediate 57, 0.2000 g, 0.628 mmol), cesium acetate (0.869 g, 4.52 mmol), 2-bromo-5-methylpyridine (0.119 g, 0.691 mmol), and dry dimethylsulfoxide (1.0 mL) was heated at 100° C. for 14 hours. Additional 2-bromo-5-methylpyridine (0.119 g, 0.691 mmol) and copper (7.99 mg, 0.126 mmol) were added to the mixture and the reaction was continued for an additional 14 hours. The mixture was diluted with ethyl acetate and ammonium hydroxide and the phases separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The crude product was purified by silica gel chromatography (0-100% ethyl acetate in hexane gradient) to give 3,3-dimethyl-1-(1-(5-methylpyridin-2-yl)piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one (0.052 g, 0.155 mmol, 24.6% yield). M+1: 337.0. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.37 (s, 6 H) 1.72-1.84 (m, 2 H) 2.20 (s, 3 H) 2.72-3.01 (m, 4 H) 4.40 (d, J=12.52 Hz, 2 H) 4.54 (tt, J=11.93, 3.91 Hz, 1 H) 6.66 (d, J=8.61 Hz, 1 H) 6.92 (dd, J=7.24, 5.28 Hz, 1 H) 7.31 (dd, J=8.61, 1.76 Hz, 1 H) 7.41 (dd, J=7.24, 1.37 Hz, 1 H) 8.02 (s, 1 H) 8.12 (dd, J=5.18, 1.27 Hz, 1 H).

後処理

  1. customthe phases separated
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by silica gel chromatography (0-100% ethyl acetate in hexane gradient)

出典と根拠

ORDレコード
ord-ca9a2f4383fe4c6e9fa9da0c09da5708
出典データセット
uspto-grants-2015_11
特許番号
US09174992B2

反応ノート

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