4-((6-(5-(methylsulfonyl)-1H-indol-1-yl)pyridin-3-yl)oxy)piperidine-1-carbonitrile → 3-isopropyl-5-(4-((6-(5-(methylsulfonyl)-1H-indol-1-yl)pyridin-3-yl)oxy)piperidin-1-yl)-1,2,4-oxadiazole

HRID 1468016Notes

Reaction equation

HRID 1468016 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[N:19]=[CH:18][C:17]([O:20][CH:21]3[CH2:26][CH2:25][N:24]([C:27]#[N:28])[CH2:23][CH2:22]3)=[CH:16][CH:15]=1)[CH:9]=[CH:8]2)(=[O:4])=[O:3].[OH:29][NH:30][C:31](=N)[CH:32]([CH3:34])[CH3:33]>C1COCC1.[Cl-].[Zn+2].[Cl-]>[CH:32]([C:31]1[N:28]=[C:27]([N:24]2[CH2:25][CH2:26][CH:21]([O:20][C:17]3[CH:18]=[N:19][C:14]([N:10]4[C:11]5[C:7](=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:13][CH:12]=5)[CH:8]=[CH:9]4)=[CH:15][CH:16]=3)[CH2:22][CH2:23]2)[O:29][N:30]=1)([CH3:34])[CH3:33]

Participants

5

Reactant 2

HCID 866961864-((6-(5-(methylsulfonyl)-1H-indol-1-yl)pyridin-3-yl)oxy)piperidine-1-carbonitrileHCID 178449908HCID 178449908, compound

Product 1

HCID 676164503-isopropyl-5-(4-((6-(5-(methylsulfonyl)-1H-indol-1-yl)pyridin-3-yl)oxy)piperidin-1-yl)-1,2,4-oxadiazoleYield 31.5%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 4-((6-(5-(methylsulfonyl)-1H-indol-1-yl)pyridin-3 yl)oxy)piperidine-1-carbonitrile (intermediate-36) (0.110 g, 0.27 mmol) and N-hydroxy-isobutyramidine (0.05 g, 0.5 mmol) in anhydrous THF (15 mL), 1M solution of zinc chloride in THF (0.56 mL, 0.56 mmol) was added. The suspension was stirred at room temperature for 18 h. Solvent was concentrated in vacuo, the resulting crude was dissolved in 4N HCl in ethanol, water (1:1) and stirred at 60-70° C. for 2-3 h. The reaction was quenched by saturated NaHCO3 and the organic layer was separated and concentrated. The residue was purified by flash column chromatography to give 3-isopropyl-5-(4-((6-(5-(methylsulfonyl)-1H-indol-1-yl)pyridin-3-yl)oxy)piperidin-1-yl)-1,2,4-oxadiazole (0.041 g, 30%)

Workup

  1. additionwas added
  2. concentrationSolvent was concentrated in vacuo
  3. dissolutionthe resulting crude was dissolved in 4N HCl in ethanol
  4. stirringwater (1:1) and stirred at 60-70° C. for 2-3 h
  5. customThe reaction was quenched by saturated NaHCO3
  6. customthe organic layer was separated
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-b3cb6f59d54d47b085f3c2946974721c
Source dataset
uspto-grants-2015_04
Patent number
US09000175B2

Reaction notes

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