Acetonitrile → [1-ethyl-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-1H-pyrazol-3-yl]-(4-fluoro-benzyl)-amine

HRID 1024239Notes

Reaction equation

HRID 1024239 reaction equation
[CH2:1]([N:3]1[C:7]([CH:8](OC)[C:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[NH:11][CH:10]=2)=[CH:6][C:5]([NH:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)=[N:4]1)[CH3:2].C(#N)C.C([SiH](CC)CC)C.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[CH2:1]([N:3]1[C:7]([CH2:8][C:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[NH:11][CH:10]=2)=[CH:6][C:5]([NH:20][CH2:21][C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)=[N:4]1)[CH3:2]

Participants

7

Reactant 5

HCID 6342AcetonitrileHCID 6422Trifluoroacetic acid2×HCID 11430Potassium CarbonateHCID 12052Triethylsilane2×HCID 576194351-ethyl-5-[methoxy-(1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-1H-pyrazol-3-yl-(4-fluoro-benzyl)-amine

Product 1

HCID 57619179[1-ethyl-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-1H-pyrazol-3-yl]-(4-fluoro-benzyl)-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To 1-ethyl-5-[methoxy-(1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-1H-pyrazol-3-yl-(4-fluoro-benzyl)-amine (531, 0.12 g, 0.32 mmol) in acetonitrile (10.0 mL, 0.191 mol) were added triethylsilane (0.60 mL, 0.0038 mol) and trifluoroacetic acid (0.30 mL, 0.0039 mol). The reaction was stirred at 80° C. for 2 hours. The reaction was poured into aqueous potassium carbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and washed with ethyl acetate and hexane to give crude compound. 1H NMR indicated that the reaction was incomplete. The crude compound was dissolved in dichloromethane (15.0 mL), trifluoroacetic acid (0.30 mL) and triethylsilane (0.60 mL). The reaction was stirred at 43° C. for 72 hours. The reaction was concentrated, poured into aqueous potassium carbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and washed with ethyl acetate and hexane to give an off-white solid (P-0165, 18.7 mg, 17%). MS (ESI) [M+H+]+=350.3.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. washwashed with ethyl acetate and hexane
  6. customto give crude compound
  7. stirringThe reaction was stirred at 43° C. for 72 hours
  8. concentrationThe reaction was concentrated
  9. additionpoured into aqueous potassium carbonate
  10. extractionextracted with ethyl acetate
  11. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationThe filtrate was concentrated
  14. washwashed with ethyl acetate and hexane
  15. customto give an off-white solid (P-0165, 18.7 mg, 17%)

Sources & evidence

ORD record
ord-60807b4517be4d7981d62a6a7d84a735
Source dataset
uspto-grants-2014_05
Patent number
US08722702B2

Reaction notes

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