Cesium fluoride → Methyl 3-amino-6-bromo-6'-methoxy-2,3'-bipyridine-4-carboxylate

HRID 2410684Notes

Reaction equation

HRID 2410684 reaction equation
[NH2:1][C:2]1[C:11](Br)=[N:10][C:9]([Br:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH3:14][O:15][C:16]1[N:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1.[F-].[Cs+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:1][C:2]1[C:11]([C:19]2[CH:20]=[N:21][C:16]([O:15][CH3:14])=[CH:17][CH:18]=2)=[N:10][C:9]([Br:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 53419616Methyl 3-amino-2,6-dibromoisonicotinate

Product 1

HCID 86663007Methyl 3-amino-6-bromo-6'-methoxy-2,3'-bipyridine-4-carboxylateYield 50.3%

Reagents, catalysts & solvents 1

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
80 °C

Procedure

A mixture of methyl 3-amino-2,6-dibromoisonicotinate (300 mg, 0.97 mmol), 6-methoxypyridin-3-ylboronic acid (163 mg, 1.07 mmol), tetrakis(triphenylphosphine)-palladium(0) (56 mg, 0.048 mmol) and cesium fluoride (323 mg, 2.13 mmol) in a vial was flushed with nitrogen. Dimethoxyethane (4.8 mL) was added and the reaction was heated at 80° C. overnight. It was partitioned between ethyl acetate and a saturated aqueous solution of sodium bicarbonate. The organic phase was separated, washed with brine, and dried with sodium sulfate. The solvent removed and the major product was isolated by silica gel radial chromatography (step gradient with hexane containing 5 to 20% ethyl acetate). This gave methyl 3-amino-6-bromo-6′-methoxy-2,3′-bipyridine-4-carboxylate (165 mg, 50% yield) as a yellow solid. MS (ESI) m/z 338 and 340 (M+H). 1H NMR (CDCl3) δ ppm 8.45 (1H, d, J=2.14 Hz), 7.82 (1H, dd, J=8.55, 2.44 Hz), 7.80 (1H, s), 6.85 (1H, d, J=8.55 Hz), 5.91 (2H, br. s.), 3.97 (3H, s), 3.92 (3H, s).

Workup

  1. customwas flushed with nitrogen
  2. additionDimethoxyethane (4.8 mL) was added
  3. customIt was partitioned between ethyl acetate
  4. customThe organic phase was separated
  5. washwashed with brine
  6. dry with materialdried with sodium sulfate
  7. customThe solvent removed
  8. customthe major product was isolated by silica gel radial chromatography (step gradient with hexane containing 5 to 20% ethyl acetate)

Sources & evidence

ORD record
ord-c79e7ae91cd949caaadba0f65f1fc16b
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

Loading…