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

HRID 510008Notes

Reaction equation

HRID 510008 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=[C:13]3[C:12]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]([NH2:28])=[N:25][C:26]=3[F:27])=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:29][C:30]1[CH:31]=[C:32]([CH:38]=O)[C:33]([O:36][CH3:37])=[N:34][CH:35]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(#N)C>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=[C:13]3[C:12]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]([NH:28][CH2:38][C:32]4[C:33]([O:36][CH3:37])=[N:34][CH:35]=[C:30]([F:29])[CH:31]=4)=[N:25][C:26]=3[F:27])=[CH:11]2)(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 226783235-Fluoro-2-methoxynicotinaldehydeHCID 67201069HCID 67201069, compound

Product 1

HCID 67199844[5-(1-benzenesulfonyl-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-6-fluoro-pyridin-2-yl]-(5-fluoro-2-methoxy-pyridin-3-ylmethyl)-amineYield 82.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To 5-(1-benzenesulfonyl-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-6-fluoro-pyridin-2-ylamine (167, 0.342 g, 0.741 mmol) in 10 mL of acetonitrile, 5-fluoro-2-methoxy-pyridine-3-carbaldehyde (37, 0.118 g, 0.763 mmol), triethylsilane (0.529 mL, 3.71 mmol) and trifluoroacetic acid (0.286 mL, 3.71 mmol) were added. The reaction was heated at 80° C. for 4 hours, then concentrated under vacuum and combined with aqueous potassium carbonate and extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with ethyl acetate and hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as an off-white solid (168, 367 mg). MS (ESI) [M−H+]−=599.6 and 601.6.

Workup

  1. concentrationconcentrated under vacuum
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under vacuum
  7. customThe resulting material was purified by silica gel column chromatography
  8. washeluting with ethyl acetate and hexane
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-8990c30ad0e144f88a4bf99299cc12f0
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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