Trifluoroacetic acid → 3-methoxy-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamine

HRID 509976Notes

Reaction equation

HRID 509976 reaction equation
C(OC(=O)[N:7]([C:17]1[C:22]([O:23][CH3:24])=[CH:21][C:20]([CH:25](O)[C:26]2[C:34]3[C:29](=[N:30][CH:31]=[C:32]([CH3:35])[CH:33]=3)[NH:28][CH:27]=2)=[CH:19][N:18]=1)CC1C=CC(OC)=CC=1)(C)(C)C.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(#N)C>[CH3:24][O:23][C:22]1[C:17]([NH2:7])=[N:18][CH:19]=[C:20]([CH2:25][C:26]2[C:34]3[C:29](=[N:30][CH:31]=[C:32]([CH3:35])[CH:33]=3)[NH:28][CH:27]=2)[CH:21]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 58259011{5-[hydroxy-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-3-methoxy-pyridin-2-yl}-(4-methoxy-benzyl)-carbamic acid tert-butyl ester

Product 1

HCID 582593253-methoxy-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

In a round bottom flask, {5-[hydroxy-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-3-methoxy-pyridin-2-yl}-(4-methoxy-benzyl)-carbamic acid tert-butyl ester (127, 1 equivalent) is combined with 100 mL of acetonitrile, triethylsilane (18 equivalents), and trifluoroacetic acid (18 equivalents). The reaction is heated at reflux for 24 hours, then concentrated under vacuum. The resulting material is dissolved in 40 mL of trifluoroacetic acid and stirred at room temperature for 18 hours. This is concentrated under vacuum and combined with water and sodium bicarbonate, then extracted with ethyl acetate. The organic layer is washed with sodium bicarbonate, water, brine, then dried with magnesium sulfate, filtered and the filtrate is concentrated under vacuum. The resulting material is purified by silica gel column chromatography eluting with ethyl acetate and hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound.

Workup

  1. temperatureThe reaction is heated
  2. temperatureat reflux for 24 hours
  3. concentrationconcentrated under vacuum
  4. dissolutionThe resulting material is dissolved in 40 mL of trifluoroacetic acid
  5. concentrationThis is concentrated under vacuum
  6. extractionextracted with ethyl acetate
  7. washThe organic layer is washed with sodium bicarbonate, water, brine
  8. dry with materialdried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate is concentrated under vacuum
  11. customThe resulting material is purified by silica gel column chromatography
  12. washeluting with ethyl acetate and hexane
  13. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-b43e9ad5df00491aa4eb6630f849001a
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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