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

HRID 1024159Notes

Reaction equation

HRID 1024159 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 (6-Chloro-pyridin-3-yl)-(1H-pyrrolo[2,3-b]pyridin-3-yl)-methanone 7 (3.5 g, 0.014 mol, prepared as described in Example 3), 4-(trifluoromethyl)benzylamine (30, 9.0 g, 0.051 mol), tetrahydrofuran (30.0 mL, 0.37 mol), 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° C. overnight, poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated. To the residue was added acetic acid (15.0 mL) and H2O (5.0 mL). The reaction mixture was stirred at 100° C. for 5 hours and concentrated to remove the 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 compound P-0017 (1.0 g, yield=18.5%) as a light yellow solid. MS (ESI) [M+H]+=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° C. for 5 hours
  7. concentrationconcentrated
  8. customto remove the 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
  15. customto give compound P-0017 (1.0 g, yield=18.5%) as a light yellow solid

Sources & evidence

ORD record
ord-4c42a1f4c99c4a1d8f6fa492742d388a
Source dataset
uspto-grants-2014_05
Patent number
US08722702B2

Reaction notes

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