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

HRID 1895737Notes

Reaction equation

[OH:1][C:2]1[C:3]([C:9]#[N:10])=[CH:4][NH:5][C:6](=[O:8])[CH:7]=1.Br[C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=1.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:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=2)[C:6](=[O:8])[CH:7]=1

Participants

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-(methylsulfonyl)benzene (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

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

Sources & evidence

ORD record: ord-cdc2134a90274c84b5e5693d10edf8e7
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513424B2

Reaction notes

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