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

HRID 707335노트

반응식

HRID 707335 반응식
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]

참가 물질

8

반응물 4

HCID 679Dimethyl SulfoxideHCID 5642162-Bromo-5-methylpyridine2회HCID 5152919Cesium acetateHCID 866941923,3-dimethyl-1-(piperidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one dihydrochloride2회

생성물 1

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

시약·촉매·용매 3

HCID 23978Copper촉매HCID 8857Ethyl Acetate용매HCID 14923Ammonium Hydroxide용매

반응 조건

온도
100 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-ca9a2f4383fe4c6e9fa9da0c09da5708
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09174992B2

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