Acetic Anhydride → N-(5-{(1E)-3-Oxo-3-[3-(pyridin-4-ylmethoxy)azetidin-1-yl]prop-1-en-1-yl}pyridin-2-yl)acetamide

HRID 2172026Notes

Reaction equation

HRID 2172026 reaction equation
[O:1]=[C:2]([N:12]1[CH2:15][CH:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)[CH2:13]1)/[CH:3]=[CH:4]/[C:5]1[CH:6]=[CH:7][C:8]([NH2:11])=[N:9][CH:10]=1.[C:24](OC(=O)C)(=[O:26])[CH3:25].C([O-])(O)=O.[Na+]>C1COCC1>[O:1]=[C:2]([N:12]1[CH2:13][CH:14]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=2)[CH2:15]1)/[CH:3]=[CH:4]/[C:5]1[CH:6]=[CH:7][C:8]([NH:11][C:24](=[O:26])[CH3:25])=[N:9][CH:10]=1

Participants

5

Reactant 3

HCID 7918Acetic Anhydride2×HCID 516892Sodium Bicarbonate2×HCID 529505295-{(1E)-3-Oxo-3-[3-(pyridin-4-ylmethoxy)azetidin-1-yl]prop-1-en-1-yl}pyridin-2-amine

Product 1

HCID 52950530N-(5-{(1E)-3-Oxo-3-[3-(pyridin-4-ylmethoxy)azetidin-1-yl]prop-1-en-1-yl}pyridin-2-yl)acetamideYield 13.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 5-{(1E)-3-oxo-3-[3-(pyridin-4-ylmethoxy)azetidin-1-yl]prop-1-en-1-yl}pyridin-2-amine (16 mg, 0.05 mmol) and acetic anhydride (6 μL, 0.06 mmol) in THF (2.4 mL) was added NaHCO3 (5.5 mg, 0.065 mmol). The reaction mixture was warmed at 60° C. and stirred for 40 h. LCMS showed that some starting material was remaining. Another portion of acetic anhydride (6 μL) and NaHCO3 (5.5 mg) were added and the mixture was stirred at 60° C. for 24 h. These additions were repeated twice over 48 h. The mixture was then concentrated, partitioned between water and ethyl acetate. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed wih brine, dried over sodium sulfate, filtered and concentrated under vacuum to give an oil. The crude was purified on preparative TLC (eluent: 90/10 DCM/MeOH) to give the title compound (2.3 mg, 12%) as a pale yellow solid.

Workup

  1. stirringthe mixture was stirred at 60° C. for 24 h
  2. waitThese additions were repeated twice over 48 h
  3. concentrationThe mixture was then concentrated
  4. custompartitioned between water and ethyl acetate
  5. extractionThe aqueous layer was extracted twice with ethyl acetate
  6. washThe combined organic layers were washed wih brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customto give an oil
  11. customThe crude was purified on preparative TLC (eluent: 90/10 DCM/MeOH)

Sources & evidence

ORD record
ord-425b43d78f974a9ca9810fdc5fdac307
Source dataset
uspto-grants-2015_06
Patent number
US09051321B2

Reaction notes

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