Pyridine → 5-BROMO-N-PHENYLNICOTINAMIDE

HRID 876225Notes

Reaction equation

HRID 876225 reaction equation
N1C=CC=CC=1.[Br:7][C:8]1[CH:9]=[C:10]([C:14](Cl)=[O:15])[CH:11]=[N:12][CH:13]=1.[NH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C)C1C=CN=CC=1.CN(C=O)C.O1CCCC1>[Br:7][C:8]1[CH:9]=[C:10]([C:14]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH:11]=[N:12][CH:13]=1

Participants

7

Reactant 3

HCID 1049PyridineHCID 6115AnilineHCID 27812235-Bromonicotinoyl chloride

Product 1

HCID 42730445-BROMO-N-PHENYLNICOTINAMIDE

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under argon and at RT, 32.4 ml (400 mmol, 2 eq.) of pyridine, 2.4 g (20 mmol, 0.1 eq.) of 4-dimethylaminopyridine and, dropwise, a solution of 44.1 g (200 mmol, 1.0 eq.) of 5-bromopyridine-3-carbonyl chloride in 200 ml of DMF were added to a solution of 18.6 g (200 mmol) of aniline in 500 ml of tetrahydrofuran. After 3 h, the reaction mixture was concentrated under reduced pressure. The residue was suspended in water/dichloromethane and the solid was stirred well, washed repeatedly with water and dichloromethane and dried under reduced pressure. Yield: 35.7 g (52% of theory) After phase separation of the mother liquor, the organic phase was extracted twice with dichloromethane. The combined organic phases were dried (sodium sulphate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, dichloromethane/methanol 100:1), which gave 11.7 g (18% of theory) of Example 14A.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. washwashed repeatedly with water and dichloromethane
  3. customdried under reduced pressure
  4. customYield: 35.7 g (52% of theory) After phase separation of the mother liquor
  5. extractionthe organic phase was extracted twice with dichloromethane
  6. dry with materialThe combined organic phases were dried (sodium sulphate)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography (silica gel, dichloromethane/methanol 100:1), which
  10. customgave 11.7 g (18% of theory) of Example 14A

Sources & evidence

ORD record
ord-13b404e1bfe7402289c7be48793cf482
Source dataset
uspto-grants-2015_03
Patent number
US08987248B2

Reaction notes

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