Trifluoroacetic acid → 6-[(5-Fluoro-2-methoxy-pyridin-3-ylmethyl)-amino]-nicotinic acid methyl ester

HRID 509958Notes

Reaction equation

HRID 509958 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[N:6][CH:5]=1.[F:12][C:13]1[CH:14]=[C:15]([CH:21]=O)[C:16]([O:19][CH3:20])=[N:17][CH:18]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>O.C(#N)C>[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:21][C:15]2[C:16]([O:19][CH3:20])=[N:17][CH:18]=[C:13]([F:12])[CH:14]=2)=[N:6][CH:5]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 737487Methyl 6-aminonicotinateHCID 226783235-Fluoro-2-methoxynicotinaldehyde

Product 1

HCID 582593336-[(5-Fluoro-2-methoxy-pyridin-3-ylmethyl)-amino]-nicotinic acid methyl esterYield 83.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

In a round bottom flask, 6-amino-nicotinic acid methyl ester (90, 0.678 g, 4.46 mmol) was combined with 5-fluoro-2-methoxy-pyridine-3-carbaldehyde (37, 0.532 g, 3.43 mmol), 10.6 mL of acetonitrile, trifluoroacetic acid (1.32 mL, 17.1 mmol) and triethylsilane (3.29 mL, 20.6 mol). The reaction was heated to reflux for 3 hours, then 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 and hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (91, 832 mg). MS (ESI) [M+H+]+=292.4.

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 and hexane
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-16c75dc76188463eafa7abddfec65761
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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