Tetrahydrofuran → (1H-Pyrrolo[2,3-b]pyridin-3-yl)-[6-(4-trifluoromethyl-benzylamino)-pyridin-3-yl]-methanone

HRID 550955Notes

Reaction equation

HRID 550955 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[CH:16][CH:17]=3)[NH:12][CH:11]=2)=[O:9])=[CH:4][CH:3]=1.[F:19][C:20]([F:30])([F:29])[C:21]1[CH:28]=[CH:27][C:24]([CH2:25][NH2:26])=[CH:23][CH:22]=1.O1CCCC1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[NH:12]1[C:13]2=[N:14][CH:15]=[CH:16][CH:17]=[C:18]2[C:10]([C:8]([C:5]2[CH:6]=[N:7][C:2]([NH:26][CH2:25][C:24]3[CH:23]=[CH:22][C:21]([C:20]([F:19])([F:29])[F:30])=[CH:28][CH:27]=3)=[CH:3][CH:4]=2)=[O:9])=[CH:11]1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 768044-(Trifluoromethyl)benzylamineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 57588066(6-Chloro-pyridin-3-yl)-(1H-pyrrolo[2,3-b]pyridin-3-yl)-methanone

Product 1

HCID 11632642(1H-Pyrrolo[2,3-b]pyridin-3-yl)-[6-(4-trifluoromethyl-benzylamino)-pyridin-3-yl]-methanoneYield 18.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Conditions

Temperature
180 °C

Procedure

Into a pressure flask was added compound 7 (3.5 g, 0.014 mol) and 4-(trifluoromethyl)benzylamine (9.0 g, 0.051 mol) and tetrahydrofuran (30.0 mL, 0.37 mol) and palladium acetate (200.0 mg, 0.890 mmol) and 2-(di-t-butylphosphino)biphenyl (200.0 mg, 0.67 mmol). The reaction mixture was stirred at 180 Celsius overnight, poured into water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, concentrated. To the residue was added acetic acid (15.0 mL) and H2O (5.0 mL). The reaction mixture was stirred at 100 Celsius for 5 hours and concentrated to remove acetic acid. The residue was then treated with aqueous Na2HCO3 and extracted with ethyl acetate. The organic layer was washed, dried, concentrated and purified to give product 13 (1.0 g, yield=18.5%) as a light yellow solid (M+1=397).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. additionTo the residue was added acetic acid (15.0 mL) and H2O (5.0 mL)
  6. stirringThe reaction mixture was stirred at 100 Celsius for 5 hours
  7. concentrationconcentrated
  8. customto remove acetic acid
  9. additionThe residue was then treated with aqueous Na2HCO3
  10. extractionextracted with ethyl acetate
  11. washThe organic layer was washed
  12. customdried
  13. concentrationconcentrated
  14. custompurified

Sources & evidence

ORD record
ord-470deefbbec9480dab0d39ed499a8f9b
Source dataset
uspto-grants-2011_05
Patent number
US07947708B2

Reaction notes

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