Sodium Carbonate → HCID 90023446, compound

HRID 1484520Notes

Reaction equation

HRID 1484520 reaction equation
[CH3:1][C:2]1([CH3:24])[C:6]2[C:7]([O:12][C:13]3[N:18]=[CH:17][C:16]([NH:19][C:20]([NH:22][NH2:23])=[O:21])=[CH:15][CH:14]=3)=[CH:8][CH:9]=[C:10]([CH3:11])[C:5]=2[O:4][CH2:3]1.[C:25](OCC)(OCC)(OCC)[CH3:26].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])([O-])=O.[Na+].[Na+]>CCO.C(OCC)(=O)C.O>[CH3:25][C:26]1[N:19]([C:16]2[CH:17]=[N:18][C:13]([O:12][C:7]3[C:6]4[C:2]([CH3:24])([CH3:1])[CH2:3][O:4][C:5]=4[C:10]([CH3:11])=[CH:9][CH:8]=3)=[CH:14][CH:15]=2)[C:20](=[O:21])[NH:22][N:23]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 66221Triethyl orthoacetate2×HCID 521998p-Toluenesulfonic acid monohydrate2×HCID 90015121HCID 90015121, compound

Product 1

HCID 90023446HCID 90023446, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

The crude N-{6-[(3,3,7-trimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]pyridin-3-yl}hydrazinecarboxamide (330 mg, 1.0 mmol) was suspended in EtOH (4.5 mL) and triethyl orthoacetate (3 equiv) was added, followed by p-toluenesulfonic acid hydrate (0.1 equiv). The resulting solution was heated to reflux for 24 hrs and then evaporated to dryness. Since the reaction was not complete, the residue was re-dissolved in EtOH (4.5 mL), more triethyl orthoacetate (3 equiv) and p-toluenesulfonic acid hydrate (0.1 equiv) were added and the solution stirred at reflux for additional 18 hours. The mixture was cooled to room temperature and diluted with ethyl acetate and water. Saturated Na2CO3 solution was added the layers were separated and the organic washed with brine, dried over Na2SO4 and evaporated to dryness. The residue was purified via silica chromatography, eluting with cyclohexane/ethyl acetate from 5/5 to 3/7. The fractions containing the product were combined and evaporated to dryness. The residue was further purified by triturating with methyl tert-butyl ether/n-heptanes. The solid was collected and washed with n-heptanes to afford 5-methyl-4-{6-[(3,3,7-trimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]pyridin-3-yl}-2,4-dihydro-3H-1,2,4-triazol-3-one as a white solid (177 mg).

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux for 24 hrs
  3. customevaporated to dryness
  4. dissolutionthe residue was re-dissolved in EtOH (4.5 mL)
  5. temperatureat reflux for additional 18 hours
  6. customwere separated
  7. washthe organic washed with brine
  8. dry with materialdried over Na2SO4
  9. customevaporated to dryness
  10. customThe residue was purified via silica chromatography
  11. washeluting with cyclohexane/ethyl acetate from 5/5 to 3/7
  12. additionThe fractions containing the product
  13. customevaporated to dryness
  14. customThe residue was further purified
  15. customby triturating with methyl tert-butyl ether/n-heptanes
  16. customThe solid was collected
  17. washwashed with n-heptanes

Sources & evidence

ORD record
ord-4bca1c80254945d3a2d613d50ee89c33
Source dataset
uspto-grants-2016_08
Patent number
US09422252B2

Reaction notes

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