Water → 5'-Fluoro-5-nitro-3,3'-bipyridin-4-amine

HRID 589460Notes

Reaction equation

HRID 589460 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([N+:9]([O-:11])=[O:10])[C:7]=1[NH2:8].[F:12][C:13]1[CH:14]=[N:15][CH:16]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:18]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>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.CN(C=O)C>[F:12][C:13]1[CH:18]=[C:17]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([N+:9]([O-:11])=[O:10])[C:7]=2[NH2:8])[CH:16]=[N:15][CH:14]=1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 49975884-Amino-3-bromo-5-nitropyridineHCID 164142683-Fluoro-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

Product 1

HCID 867010655'-Fluoro-5-nitro-3,3'-bipyridin-4-amineYield 74%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 3-bromo-5-nitropyridin-4-amine (LXIX) (790 mg, 3.62 mmol), 3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (LXX) (1.01 g, 4.35 mmol), K3PO4 (1.15 g, 5.44 mmol), water (10 mL) and DMF (10 mL) was degassed with argon thrice. Pd(PPh3)4 (209 mg, 0.18 mmol) was added to the reaction and the solution was heated at 90° C. for 4 h. The reaction was passed through a pad of Celite and then concentrated under reduced pressure. The reaction mixture was concentrated and the residue was taken up in EtOAc. The organic extract was washed with water, dried and concentrated under vacuum. The crude product was purified on a silica gel column (100% CHCl3→1.5:98.5 MeOH[7N NH3]:CHCl3) to give 5′-fluoro-5-nitro-3,3′-bipyridin-4-amine (LXXI) as a yellow solid (626 mg, 2.67 mmol, 74% yield). 1H NMR (DMSO-d6, 500 MHz) δ ppm 7.62 (brs, 2H), 7.86-7.89 (m, 1H), 8.15 (s, 1H), 8.47-8.48 (m, 1H), 8.67 (d, J=2.7 Hz, 1H), 9.07 (s, 1H); ESIMS found C10H7FN4O2 m/z 235 (M+H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. concentrationThe reaction mixture was concentrated
  3. extractionThe organic extract
  4. washwas washed with water
  5. customdried
  6. concentrationconcentrated under vacuum
  7. customThe crude product was purified on a silica gel column (100% CHCl3→1.5:98.5 MeOH[7N NH3]:CHCl3)

Sources & evidence

ORD record
ord-47b76b4321c745b8a2bfc87745f014a7
Source dataset
uspto-grants-2016_01
Patent number
US09233104B2

Reaction notes

Loading…