2,2-Difluoro-1,3-benzodioxole-5-carbonyl chloride → 2,2-Difluoro-N-{5-[4-(pyridin-3-yloxy)phenyl]-1,3,4-oxadiazol-2-yl}-1,3-benzodioxole-5-carboxamide

HRID 387481

Reaction equation

HRID 387481 reaction equation
Br.[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[O:19][C:18]([NH2:20])=[N:17][N:16]=3)=[CH:11][CH:10]=2)[CH:3]=1.[F:21][C:22]1([F:34])[O:26][C:25]2[CH:27]=[CH:28][C:29]([C:31](Cl)=[O:32])=[CH:30][C:24]=2[O:23]1>N1C=CC=CC=1.CO>[F:34][C:22]1([F:21])[O:26][C:25]2[CH:27]=[CH:28][C:29]([C:31]([NH:20][C:18]3[O:19][C:15]([C:12]4[CH:11]=[CH:10][C:9]([O:8][C:4]5[CH:3]=[N:2][CH:7]=[CH:6][CH:5]=5)=[CH:14][CH:13]=4)=[N:16][N:17]=3)=[O:32])=[CH:30][C:24]=2[O:23]1

Participants

5

Reactant 2

HCID 27740642,2-Difluoro-1,3-benzodioxole-5-carbonyl chlorideHCID 686796585-[4-(Pyridin-3-yloxy)phenyl]-1,3,4-oxadiazol-2-amine hydrobromide salt

Product 1

HCID 591354562,2-Difluoro-N-{5-[4-(pyridin-3-yloxy)phenyl]-1,3,4-oxadiazol-2-yl}-1,3-benzodioxole-5-carboxamideYield 12.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent

Procedure

5-[4-(Pyridin-3-yloxy)phenyl]-1,3,4-oxadiazol-2-amine hydrobromide salt (167.5 mg, 0.5 mmol) was suspended in 2 mL of anhydrous pyridine. Neat 2,2-difluoro-1,3-benzodioxole-5-carbonyl chloride (165.4 mg, 0.75 mmol) was added directly into the solution. The reaction mixture formed an orange-red solution with a small amount of white precipitate. It was left to stir for 3 hours. Then it was diluted with ca. 1 mL of MeOH, filtered through 0.22 u syringe filter and purified by reverse phase preparative HPLC using acetonitrile/water mixture containing 0.01% of TFA. Fractions, containing the product, were combined and partitioned between ca. 40 mL of EtOAc and ca. 40 mL of saturated aqueous NaHCO3. The EtOAc layer was washed with brine, dried over anhydrous sodium sulfate and filtered. Solvent was removed in vacuo to give the title product as a yellow solid (27.0 mg). Yield 12.3%.

Workup

  1. customThe reaction mixture formed an orange-red solution with a small amount of white precipitate
  2. waitIt was left
  3. filtrationfiltered through 0.22 u syringe
  4. filtrationfilter
  5. custompurified by reverse phase preparative HPLC
  6. additioncontaining 0.01% of TFA
  7. additionFractions, containing the product
  8. custompartitioned between ca. 40 mL of EtOAc and ca. 40 mL of saturated aqueous NaHCO3
  9. washThe EtOAc layer was washed with brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. customSolvent was removed in vacuo

Sources & evidence

ORD record
ord-d25e1e59550a497c961035ec60f8b910
Source dataset
uspto-grants-2013_02
Patent number
US08372971B2

Linked notes

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