Trifluoroacetic acid → 6-fluoro-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamine

HRID 1396151Notes

Reaction equation

HRID 1396151 reaction equation
C(OC(=O)[N:7]([C:17]1[CH:22]=[CH:21][C:20]([CH:23](O)[C:24]2[C:32]3[C:27](=[N:28][CH:29]=[C:30]([CH3:33])[CH:31]=3)[N:26]([Si](C(C)C)(C(C)C)C(C)C)[CH:25]=2)=[C:19]([F:45])[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>[F:45][C:19]1[N:18]=[C:17]([NH2:7])[CH:22]=[CH:21][C:20]=1[CH2:23][C:24]1[C:32]2[C:27](=[N:28][CH:29]=[C:30]([CH3:33])[CH:31]=2)[NH:26][CH:25]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 58258936{6-fluoro-5-[hydroxy-(5-methyl-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-pyridin-2-yl}-(4-methoxy-benzyl)-carbamic acid tert-butyl ester

Product 1

HCID 582592126-fluoro-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamineYield 62.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To {6-fluoro-5-[hydroxy-(5-methyl-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-pyridin-2-yl}-(4-methoxy-benzyl)-carbamic acid tert-butyl ester (48, 21 g, 32.4 mmol) in 500 mL of acetonitrile, triethylsilane (51.7 mL, 324 mmol) and trifluoroacetic acid (24.93 mL, 324 mmol) are added. The reaction is stirred at 50° C. for several hours, then concentrated under vacuum, and the residue is taken up in 250 mL of dichloromethane and 250 mL of trifluoroacetic acid is added. The mixture is stirred at reflux for several hours, then concentrated under vacuum. The residue is taken up in ethyl acetate and poured into aqueous potassium carbonate. The organic layer is separated, concentrated under vacuum and purified by silica gel column chromatography, eluting with 0-5% methanol in dichloromethane. Appropriate fractions are combined and the solvents removed under vacuum to provide the desired compound (49, 5.2 g, 20.29 mmol, 62.7% yield).

Workup

  1. concentrationconcentrated under vacuum
  2. addition250 mL of trifluoroacetic acid is added
  3. stirringThe mixture is stirred
  4. temperatureat reflux for several hours
  5. concentrationconcentrated under vacuum
  6. additionpoured into aqueous potassium carbonate
  7. customThe organic layer is separated
  8. concentrationconcentrated under vacuum
  9. custompurified by silica gel column chromatography
  10. washeluting with 0-5% methanol in dichloromethane
  11. customthe solvents removed under vacuum

Sources & evidence

ORD record
ord-09d15cc7905c4be5ad14f196ca6f1c43
Source dataset
uspto-grants-2014_12
Patent number
US08901118B2

Reaction notes

Loading…