4-Fluorobenzoyl chloride → HCID 10020895, compound

HRID 398870Notes

Reaction equation

HRID 398870 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1.[F:18][C:19]1[CH:27]=[CH:26][C:22]([C:23](Cl)=[O:24])=[CH:21][CH:20]=1>N1C=CC=CC=1>[F:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([NH:1][C:2]2[N:7]=[C:6]3[C:8]([CH:11]4[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]4)=[CH:9][NH:10][C:5]3=[CH:4][CH:3]=2)=[O:24])=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 678794-Fluorobenzoyl chloride2×HCID 102202303-(1-Methyl-piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-ylamine

Product 1

HCID 10020895HCID 10020895, compoundYield 87.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of 1.00 gm (4.3 mMol) 5-amino-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine in 85 mL pyridine was heated to 55° C. To this solution were added 0.57 mL (4.8 mMol) 4-fluorobenzoyl chloride and the resulting mixture was stirred for 30 minutes at which time an additional 0.10 mL 4-fluorobenzoyl chloride were added. After stirring for an additional 10 minutes the reaction mixture was concentrated under reduced pressure. The residue was treated with 50 mL cold 1N sodium hydroxide followed by 100 mL dichloromethane. The phases were separated and the aqueous phase was extracted 2×50 mL dichloromethane followed by 3×50 mL 3:1 chloroform:isopropanol. The organic phases were combined, washed with saturated aqueous sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to radial chromatography (4 mm silica gel plate) eluting with dichloromethane containing 10-20% methanol and 1% ammonium hydroxide. Fractions containing product were combined and concentrated under reduced pressure. The residue was crystallized from aqueous ethanol to provide 1.32 gm (87%) of the title compound as ivory crystals.

Workup

  1. additionwere added
  2. concentrationwas concentrated under reduced pressure
  3. additionThe residue was treated with 50 mL cold 1N sodium hydroxide
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted 2×50 mL dichloromethane
  6. washwashed with saturated aqueous sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. washeluting with dichloromethane containing 10-20% methanol and 1% ammonium hydroxide
  10. additionFractions containing product
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was crystallized from aqueous ethanol

Sources & evidence

ORD record
ord-df18b1f143a148c3ba0b2ce4b53dd252
Source dataset
uspto-grants-1998_10
Patent number
US05817671

Reaction notes

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