Hydrogen Bromide → 4,5-dichloro-2-fluoro-N-(2-oxo-1H-pyridin-4-yl)benzamide

HRID 1053165Notes

Reaction equation

HRID 1053165 reaction equation
C[O:2][C:3]1[CH:8]=[C:7]([NH2:9])[CH:6]=[CH:5][N:4]=1.[Cl:10][C:11]1[C:19]([Cl:20])=[CH:18][C:14]([C:15](O)=[O:16])=[C:13]([F:21])[CH:12]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.Br>CN(C=O)C.O>[Cl:10][C:11]1[C:19]([Cl:20])=[CH:18][C:14]([C:15]([NH:9][C:7]2[CH:6]=[CH:5][NH:4][C:3](=[O:2])[CH:8]=2)=[O:16])=[C:13]([F:21])[CH:12]=1

Participants

8

Reactant 5

HCID 260Hydrogen BromideHCID 79724-MethylmorpholineHCID 2808912-Methoxypyridin-4-amineHCID 27740154,5-Dichloro-2-fluorobenzoic 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 867284794,5-dichloro-2-fluoro-N-(2-oxo-1H-pyridin-4-yl)benzamideYield 61.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A solution of 2-methoxypyridin-4-amine (186.2 mg, 1.5 mmol), 4,5-dichloro-2-fluoro-benzoic acid (285.1 mg, 1.36 mmol), HATU (622.4 mg, 1.64 mmol) and n-methylmorpholine (299.9 μL, 2.73 mmol) in DMF (3 mL) was stirred at room temperature for 16 hours. The reaction mixture was poured into water and extracted with ethyl acetate (3×). The organics were combined, washed with water (3×), brine and dried over Na2SO4, filtered through a short plug of silica and evaporated to dryness. The material was taken up in HBr (in acetic acid) (6.689 mL of 33% w/v, 27.28 mmol) and stirred at 95° C. for 16 h. The solution was cooled to room temperature, filtered and solid product washed with water (2×) and then ether (2×) and dried under vacuum to give 4,5-dichloro-2-fluoro-N-(2-oxo-1H-pyridin-4-yl)benzamide (250 mg, 61%) as an off white solid. ESI-MS m/z calc. 299.99. found 301.3 (M+1)+; Retention time: 1.16 minutes (3 minutes run).

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washwashed with water (3×), brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered through a short plug of silica
  5. customevaporated to dryness
  6. temperatureThe solution was cooled to room temperature
  7. filtrationfiltered
  8. washsolid product washed with water (2×)
  9. dry with materialether (2×) and dried under vacuum

Sources & evidence

ORD record
ord-9aef7dd33a9b4de6a6c5ff0c2aed4bdc
Source dataset
uspto-grants-2016_07
Patent number
US09393235B2

Reaction notes

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