Cesium fluoride → Methyl 3-amino-6'-methoxy-6-(4-methoxyphenyl)-2,3'-bipyridine-4-carboxylate

HRID 2410685Notes

Reaction equation

HRID 2410685 reaction equation
[NH2:1][C:2]1[C:3]([C:13]2[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)=[N:4][C:5](Br)=[CH:6][C:7]=1[C:8]([O:10][CH3:11])=[O:9].[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.[F-].[Cs+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[C:3]([C:13]2[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)=[N:4][C:5]([C:26]2[CH:27]=[CH:28][C:23]([O:22][CH3:21])=[CH:24][CH:25]=2)=[CH:6][C:7]=1[C:8]([O:10][CH3:11])=[O:9]

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 201262(4-Methoxyphenyl)boronic acidHCID 86663007Methyl 3-amino-6-bromo-6'-methoxy-2,3'-bipyridine-4-carboxylate

Product 1

HCID 66604594Methyl 3-amino-6'-methoxy-6-(4-methoxyphenyl)-2,3'-bipyridine-4-carboxylateYield 68%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

A mixture of methyl 3-amino-6-bromo-6′-methoxy-2,3′-bipyridine-4-carboxylate (165 mg, 0.49 mmol), 4-methoxyphenylboronic acid (89 mg, 0.59 mmol), cesium fluoride (178 mg, 1.17 mmol) and tetrakis(triphenylphosphine)palladium(0) (28 mg, 0.024 mmol) in a vial was flushed with nitrogen. Dimethoxyethane (2.4 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′-methoxy-6-(4-methoxyphenyl)-2,3′-bipyridine-4-carboxylate (121 mg, 68% yield) as a yellow solid. MS (ESI) m/z 366.1 (M+H). 1H NMR (CDCl3) δ ppm 8.57 (1H, d, J=2.44 Hz), 8.05 (1H, s), 7.96 (1H, dd, J=8.55, 2.44 Hz), 7.88-7.93 (2H, m), 6.92-6.97 (2H, m), 6.88 (1H, d, J=8.55 Hz), 5.88 (2H, s), 4.00 (3H, s), 3.96 (3H, s), 3.84 (3H, s).

Workup

  1. customwas flushed with nitrogen
  2. additionDimethoxyethane (2.4 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-c5eff5ddc3364059bcafca5b42907102
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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