Tetrahydrofuran → 3-(3-amino-2,6-difluoro-benzoyl)-4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile

HRID 1187297Notes

Reaction equation

HRID 1187297 reaction equation
[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[NH:10][CH:11]=[C:12]([C:13](=[O:25])[C:14]3[C:19]([F:20])=[CH:18][CH:17]=[C:16]([N+:21]([O-])=O)[C:15]=3[F:24])[C:3]=12.[Sn](Cl)Cl.O1CCCC1.C(=O)(O)[O-].[Na+]>C(O)C.C(OCC)(=O)C.O>[NH2:21][C:16]1[C:15]([F:24])=[C:14]([C:19]([F:20])=[CH:18][CH:17]=1)[C:13]([C:12]1[C:3]2[C:4](=[N:5][CH:6]=[C:7]([C:8]#[N:9])[C:2]=2[Cl:1])[NH:10][CH:11]=1)=[O:25]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 24479Stannous ChlorideHCID 516892Sodium BicarbonateHCID 671744844-chloro-3-(2,6-difluoro-3-nitro-benzoyl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile

Product 1

HCID 671738353-(3-amino-2,6-difluoro-benzoyl)-4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carbonitrileYield 88%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

In a round bottom flask, 4-chloro-3-(2,6-difluoro-3-nitro-benzoyl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile (51, 0.15 g, 0.42 mmol) in 10 mL of ethanol and 10 mL of tetrhydrofuran, tin(II) chloride (0.1 mL, 2.1 mmol) is added. An additional 10 mL of tetrahydrofuran is added to give a clear solution, and the reaction is heated at 60° C. for 24 hours. The reaction is combined with 10 mL of water and 10 mL of saturated aqueous sodium bicarbonate and 20 mL of ethyl acetate is added. Celite is added with mixing, and then filtered. Brine is added to the filtrate and the layers are separated. The organic layer is washed with water, brine, dried with magenesium sulfate, filtered and the filtrate is concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with 0-80% ethyl acetate in hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (52, 123 mg). MS (ESI) [M+H+]+=332.8 and 334.8.

Workup

  1. customto give a clear solution
  2. additionis added
  3. additionCelite is added
  4. additionwith mixing
  5. filtrationfiltered
  6. additionBrine is added to the filtrate
  7. customthe layers are separated
  8. washThe organic layer is washed with water, brine
  9. dry with materialdried with magenesium sulfate
  10. filtrationfiltered
  11. concentrationthe filtrate is concentrated under vacuum
  12. customThe resulting material is purified by silica gel column chromatography
  13. washeluting with 0-80% ethyl acetate in hexane
  14. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-12cbf5716d9843f9b81c261c9af95409
Source dataset
uspto-grants-2014_03
Patent number
US08673928B2

Reaction notes

Loading…