Hydrochloric Acid → 4-Hydroxy-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridine-3-carbonitrile

HRID 1676211Notes

Reaction equation

HRID 1676211 reaction equation
[OH:1][C:2]1[C:3]([C:9]#[N:10])=[CH:4][NH:5][C:6](=[O:8])[CH:7]=1.[CH3:11][S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:14])=[O:13].COC1C2C(=C3C(=CC=2)C(OC)=CC=N3)N=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O.[Cu]I.O>[OH:1][C:2]1[C:3]([C:9]#[N:10])=[CH:4][N:5]([C:18]2[CH:19]=[CH:20][C:15]([S:12]([CH3:11])(=[O:14])=[O:13])=[CH:16][CH:17]=2)[C:6](=[O:8])[CH:7]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 18369Methyl phenyl sulfoneHCID 104622984,7-Dimethoxy-1,10-phenanthrolineHCID 547063254,6-Dihydroxynicotinonitrile

Product 1

HCID 673687684-Hydroxy-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridine-3-carbonitrileYield 5.74%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
190 °C

Procedure

A mixture of 4-hydroxy-6-oxo-1,6-dihydropyridine-3-carbonitrile (200 mg, 1.469 mmol, Medinoah), 1-bromo-4-(methylsulfonylbenzene (345 mg, 1.469 mmol), 4,7-dimethoxy-1,10-phenanthroline (70.6 mg, 0.294 mmol), copper(I) iodide (56.0 mg, 0.294 mmol) and potassium carbonate (609 mg, 4.41 mmol) in DMSO (3 mL) was heated at 190° C. To the reaction mixture was added H2O (10 mL) and the pH adjusted to ˜2 using with 1N HCl. The resulting aqueous mixture was extracted with EtOAc (40 mL, 2×). The combined extracts were dried over Na2SO4 and concentrated to give a brown oil. The crude oil was purified by flash chromatography (SiO2, 0-5% MeOH/CH2Cl2) to give a yellow solid (35 mg, 0.084 mmol, 5.74%). MS (ESI) 291 (M+H).

Workup

  1. extractionThe resulting aqueous mixture was extracted with EtOAc (40 mL, 2×)
  2. dry with materialThe combined extracts were dried over Na2SO4
  3. concentrationconcentrated
  4. customto give a brown oil
  5. customThe crude oil was purified by flash chromatography (SiO2, 0-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-b2b9f058cc5a4c0599dc789b8139d968
Source dataset
uspto-grants-2011_08
Patent number
US08003796B2

Reaction notes

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