Triethylamine → Methyl thieno[2,3-b]pyridine-2-carboxylate

HRID 57159

Reaction equation

HRID 57159 reaction equation
Cl[C:2]1[C:7]([CH:8]=O)=[CH:6][CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.[C:17]([O:21][CH3:22])(=[O:20])[CH2:18][SH:19]>CC#N>[CH3:22][O:21][C:17]([C:18]1[S:19][C:2]2=[N:3][CH:4]=[CH:5][CH:6]=[C:7]2[CH:8]=1)=[O:20]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 16907Methyl ThioglycolateHCID 7376072-Chloro-3-pyridinecarboxaldehyde

Product 1

HCID 19007380Methyl thieno[2,3-b]pyridine-2-carboxylateYield 29%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To 2-chloro-3-pyridine carboxaldehyde, compound 147-A, (5.07 g, 35.8 mmol), dissolved in MeCN (30 mL) was added triethylamine (6.5 mL, 46.5 mmol) followed by methyl thioglycolate (3.49 mL, 38.3 mmol) and the reaction was refluxed for 18 h. The reaction mixture was cooled and the solvent evaporated under reduced pressure. The crude residue was partitioned between H2O and EtOAc, the layers separated and the aqueous phase extracted with EtOAc. The organic layers were combined, washed with H2O, brine, dried over Na2SO4, filtered, and the solvent evaporated under reduced pressure. The crude residue was purified by flash column chromatography (SiO2) eluting with a heptane-EtOAc gradient to afford compound 147-B as a white solid (2.01 g, 29%). 1H-NMR (DMSO-d6): δ 3.91 (s, 3H), 7.54-7.57 (m, 1H), 8.23 (s, 1H), 8.43-8.46 (m, 1H), 8.72-8.74 (m, 1H); MS: m/z 194.1 (MH+).

Workup

  1. temperaturethe reaction was refluxed for 18 h
  2. temperatureThe reaction mixture was cooled
  3. customthe solvent evaporated under reduced pressure
  4. customThe crude residue was partitioned between H2O and EtOAc
  5. customthe layers separated
  6. extractionthe aqueous phase extracted with EtOAc
  7. washwashed with H2O, brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customthe solvent evaporated under reduced pressure
  11. customThe crude residue was purified by flash column chromatography (SiO2)
  12. washeluting with a heptane-EtOAc gradient

Sources & evidence

ORD record
ord-faca6572fb7d4da286b28a4a3864a888
Source dataset
uspto-grants-2016_09
Patent number
US09434711B2

Linked notes

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