Dimethyl Sulfoxide → 3'-fluoro-4'-iodo-3-[(4-methoxybenzyl)oxy]-4H-1,2'-bipyridin-4-one

HRID 571060Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:17]=[CH:16][C:6]([CH2:7][O:8][C:9]2[C:14](=[O:15])[CH:13]=[CH:12][NH:11][CH:10]=2)=[CH:5][CH:4]=1.C(=O)([O-])[O-].[K+].[K+].F[C:25]1[C:30]([F:31])=[C:29]([I:32])[CH:28]=[CH:27][N:26]=1.CS(C)=O>C(OCC)(=O)C>[F:31][C:30]1[C:25]([N:11]2[CH:12]=[CH:13][C:14](=[O:15])[C:9]([O:8][CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:17][CH:16]=3)=[CH:10]2)=[N:26][CH:27]=[CH:28][C:29]=1[I:32]

Participants

Conditions

Temperature: 85 °C

Procedure

To a 20 mL microwave vial (Biotage) was added 0.70 g (3.03 mmol) 3-[(4-methoxybenzyl)oxy]pyridin-4(1H)-one, 1.26 g (9.08 mmol) potassium carbonate, 1.10 g (4.54 mmol) 2,3-difluoro-4-iodopyridine and 15 mL DMSO. A yellow suspension formed and the vial was sealed and heated at 85° C. for 48 h on a heat block. The suspension was cooled, diluted with ethyl acetate, and washed twice with 10 mL brine. The organic layer was dried over sodium sulfate, filtered, and evaporated onto silica gel. Purification by flash chromatography (silica gel 0-100% hexanes/EtOAc gradient, followed by 10% MeOH in EtOAc) afforded 3′-fluoro-4′-iodo-3-[(4-methoxybenzyl)oxy]-4H-1,2′-bipyridin-4-one as a yellow solid. LCMS (M+H)+ 453.3.

Workup

customA yellow suspension formed
customthe vial was sealed
temperatureThe suspension was cooled
washwashed twice with 10 mL brine
dry with materialThe organic layer was dried over sodium sulfate
filtrationfiltered
customevaporated onto silica gel
customPurification by flash chromatography (silica gel 0-100% hexanes/EtOAc gradient, followed by 10% MeOH in EtOAc)

Sources & evidence

ORD record: ord-629918f3745641f4a06c0cb48f6a16fb
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09024032B2

Reaction notes

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