5-Bromo-2-fluoropyridine-3-boronic Acid (contains varying amounts of Anhydride) → 5-Bromo-2-fluoro-6'-methoxy-[3,4]bipyridinyl-3'-ylamine

HRID 1506026Notes

Reaction equation

[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH2:9])=[C:5](I)[CH:4]=1.[Br:11][C:12]1[CH:13]=[C:14](B(O)O)[C:15]([F:18])=[N:16][CH:17]=1>[F-].[K+].C(#N)C.O>[Br:11][C:12]1[CH:13]=[C:14]([C:5]2[CH:4]=[C:3]([O:2][CH3:1])[N:8]=[CH:7][C:6]=2[NH2:9])[C:15]([F:18])=[N:16][CH:17]=1

Participants

Conditions

Temperature: 95 °C

Procedure

A mixture of 6-methoxy-4-iodopyridin-3-amine (9.5 g, 38 mmol), 5-bromo-2-fluoropyridin-3-ylboronic acid (16.7 g, 76 mmol), and 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1.5 g, 2 mmol) in 1N aqueous potassium fluoride (95 mL) and acetonitrile (200 mL) was heated at 95° C. for 16 h. The cooled reaction mixture was diluted with water (100 mL) and extracted with DCM (3×100 mL). The combined organic layer was dried over sodium sulfate, filtered, and evaporated to afford a residue which was purified by flash chromotagraphy (silica, 120 g column, ISCO, 0-40% ethyl acetate in hexanes) to afford the title compound as a yellow/orange solid (8.0 g, 71%).

Workup

customThe cooled reaction mixture
extractionextracted with DCM (3×100 mL)
dry with materialThe combined organic layer was dried over sodium sulfate
filtrationfiltered
customevaporated
customto afford a residue which
customwas purified by flash chromotagraphy (silica, 120 g column, ISCO, 0-40% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-2eaac0808f93486293ec535add7d4622
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216980B2

Reaction notes

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