Aniline → 4-Bromo-pyridine-2-carboxylic acid phenylamide

HRID 1052011Notes

Reaction equation

HRID 1052011 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([OH:10])=O)[CH:3]=1.CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[NH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>CN(C)C=O>[C:43]1([NH:42][C:8]([C:4]2[CH:3]=[C:2]([Br:1])[CH:7]=[CH:6][N:5]=2)=[O:10])[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

6

Reactant 4

HCID 6115AnilineHCID 79724-MethylmorpholineHCID 7351504-Bromopyridine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 866958264-Bromo-pyridine-2-carboxylic acid phenylamideYield 71.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 4-bromo-pyridine-2-carboxylic acid (1.00 g, 5.00 mmol) in dimethylformamide (10 mL) was added 1-methylmorpholine (1.1 mL, 10 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uronium hexafluorophosphate (HATU) (2.37 g, 6.23 mmol). The mixture became an orange solution after 10 minutes. Aniline (0.5 mL, 5.5 mmol) was added and the solution was stirred at room temperature for 66 hours. The dimethylformamide was evaporated in vacuo and the residue was partitioned between water and ethyl acetate. The separated water layer was extracted with ethyl acetate. The combined ethyl acetate extract was washed with water and saturated sodium bicarbonate. The organic layer was dried (MgSO4), filtered and evaporated to crude 2. Chromatography on silica gel (40 g) applied in dichloromethane and eluted with hexanes:ethyl acetate (1:1) gave the title compound (0.986 g, 71%).

Workup

  1. customafter 10 minutes
  2. customThe dimethylformamide was evaporated in vacuo
  3. customthe residue was partitioned between water and ethyl acetate
  4. extractionThe separated water layer was extracted with ethyl acetate
  5. extractionThe combined ethyl acetate extract
  6. washwas washed with water and saturated sodium bicarbonate
  7. dry with materialThe organic layer was dried (MgSO4)
  8. filtrationfiltered
  9. customevaporated to crude 2
  10. washeluted with hexanes:ethyl acetate (1:1)

Sources & evidence

ORD record
ord-23bc6a8bc39243049d77b25dbe4e672c
Source dataset
uspto-grants-2016_07
Patent number
US09388176B2

Reaction notes

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