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

HRID 510004Notes

Reaction equation

HRID 510004 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C(OC(=O)[N:17]([C:27]1[CH:32]=[CH:31][C:30]([CH:33]=O)=[C:29]([F:35])[N:28]=1)[CH2:18][C:19]1[CH:20]=[N:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=1)(C)(C)C.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>O.C(#N)C>[F:35][C:29]1[N:28]=[C:27]([NH:17][CH2:18][C:19]2[CH:20]=[N:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=2)[CH:32]=[CH:31][C:30]=1[CH2:33][C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([F:1])[CH:3]=2)[NH:8][CH:9]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 207844625-Fluoro-1H-pyrrolo[2,3-b]pyridineHCID 57619209(6-Fluoro-5-formyl-pyridin-2-yl)-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester

Product 1

HCID 52935600[6-fluoro-5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-methoxy-pyridin-3-ylmethyl)-amineYield 8.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

In a round bottom flask, 5-fluoro-1H-pyrrolo[2,3-b]pyridine (155, 0.115 g, 0.845 mmol) was combined with (6-fluoro-5-formyl-pyridin-2-yl)-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester (156, 0.397 g, 1.10 mmol), 2.60 mL of acetonitrile, trifluoroacetic acid (0.325 mL, 4.22 mmol) and triethylsilane (0.810 mL, 5.07 mmol) and the reaction was heated to reflux for 3 hours. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with ethyl acetate in hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (P-1622, 28 mg). MS (ESI) [M+H+]+=382.1.

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux for 3 hours
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under vacuum
  8. customThe resulting material was purified by silica gel column chromatography
  9. washeluting with ethyl acetate in hexane
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-0423463c23934080878919d63617b117
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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