Formaldehyde → HCID 118378898, compound

HRID 931023Notes

Reaction equation

HRID 931023 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:12]([C:15]([N:17]3[CH2:22][C@@H:21]4[CH2:23][C@H:18]3[CH2:19][O:20]4)=[O:16])=[CH:13][N:14]=2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH:24](=O)[CH:25]=O.[Cl-].[NH4+:29].[CH2:30]=O.P(=O)(O)(O)O.[OH-].[Na+]>CO>[N:1]1([C:2]2[C:3]3[N:4]([C:12]([C:15]([N:17]4[CH2:22][C@@H:21]5[CH2:23][C@H:18]4[CH2:19][O:20]5)=[O:16])=[CH:13][N:14]=3)[CH:5]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=2)[CH:25]=[CH:24][N:29]=[CH:30]1

Participants

8

Reactant 6

HCID 712FormaldehydeHCID 1004Phosphoric AcidHCID 7860GlyoxalHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 118378989HCID 118378989, compound

Product 1

HCID 118378898HCID 118378898, compoundYield 5.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
70 °C

Procedure

A mixture of (8-amino-6-(trifluoromethyl)imidazo[1,2-a]pyridin-3-yl)((1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl)methanone (207 mg) and oxalaldehyde (92.0 mg) in methanol (1.0 mL) was stirred at 70° C. for 5 hr. To the reaction mixture were added methanol (2.0 mL), ammonium chloride (67.9 mg) and formaldehyde (38.1 mg), and the mixture was heated with reflux for 30 min. Phosphoric acid (0.087 mL) was added thereto, and the mixture was heated with reflux overnight. Ice water and 8N aqueous sodium hydroxide solution were added to the reaction mixture at 0° C., and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane), and then HPLC (C18, mobile phase: water/acetonitrile (containing 0.1% TFA)). To the obtained fraction was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and concentrated under reduced pressure, and the obtained solid was recrystallized from ethyl acetate/hexane to give the title compound (12.6 mg).

Workup

  1. temperaturethe mixture was heated
  2. temperaturewith reflux for 30 min
  3. temperaturethe mixture was heated
  4. temperaturewith reflux overnight
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe extract was washed with water and saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane)
  10. additionTo the obtained fraction was added saturated aqueous sodium hydrogen carbonate solution
  11. extractionthe mixture was extracted with ethyl acetate
  12. dry with materialThe extract was dried over anhydrous sodium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customthe obtained solid was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-816fa523e8f7465ba09876598fb91e6e
Source dataset
uspto-grants-2016_03
Patent number
US09296746B2

Reaction notes

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