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

HRID 707335Notes

Reaction equation

HRID 707335 reaction equation
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]

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 8857Ethyl AcetateSolventHCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
100 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-ca9a2f4383fe4c6e9fa9da0c09da5708
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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