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

HRID 509984Notes

Reaction equation

HRID 509984 reaction equation
[F:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]1[C:18]2[C:13](=[N:14][CH:15]=[C:16]([CH3:19])[CH:17]=2)[NH:12][CH:11]=1.[F:20][C:21]1[CH:22]=[C:23]([CH:29]=O)[C:24](=[O:28])[N:25]([CH3:27])[CH:26]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(#N)C>[F:20][C:21]1[CH:22]=[C:23]([CH2:29][NH:8][C:6]2[CH:5]=[CH:4][C:3]([CH2:9][C:10]3[C:18]4[C:13](=[N:14][CH:15]=[C:16]([CH3:19])[CH:17]=4)[NH:12][CH:11]=3)=[C:2]([F:1])[N:7]=2)[C:24](=[O:28])[N:25]([CH3:27])[CH:26]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 582592126-fluoro-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamineHCID 582594345-Fluoro-1-methyl-2-oxo-1,2-dihydro-pyridine-3-carbaldehyde

Product 1

HCID 672020755-fluoro-3-{[6-fluoro-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamino]methyl}-1-methyl-1H-pyridin-2-oneYield 50.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To 6-fluoro-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamine (137, 3.99 g, 15.59 mmol) and 5-fluoro-1-methyl-2-oxo-1,2-dihydro-pyridine-3-carbaldehyde (33, 2.66 g, 17.15 mmol) in 50 mL of acetonitrile, triethylsilane (9.96 mL, 62.4 mmol) and trifluoroacetic acid (4.80 mL, 62.4 mmol) were added. The reaction was stirred at 80° C. for several hours, then concentrated under vacuum and the residue was taken up in ethyl acetate and poured into aqueous potassium carbonate. The organic layer was separated, concentrated under vacuum, and the residue purified by silica gel column chromatography, eluting with 0-5% methanol in dichloromethane. Appropriate fractions were combined and concentrated under vacuum, and the residue triturated with methanol to provide the desired compound (P-2156, 3.1 g, 7.84 mmol, 50.3% yield).

Workup

  1. concentrationconcentrated under vacuum
  2. additionpoured into aqueous potassium carbonate
  3. customThe organic layer was separated
  4. concentrationconcentrated under vacuum
  5. customthe residue purified by silica gel column chromatography
  6. washeluting with 0-5% methanol in dichloromethane
  7. concentrationconcentrated under vacuum
  8. customthe residue triturated with methanol

Sources & evidence

ORD record
ord-3e3b0d8ffbf34d9aa3596efbd81b7c42
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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