Acetic Acid → N-[2-({4-[4-(3-Bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl]sulfamide

HRID 632542Notes

Reaction equation

HRID 632542 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[O:12][N:11]=[C:10]2[C:15]2[C:16]([NH:20][CH2:21][CH2:22][NH:23][S:24]([NH:27]C(=O)OCC(Cl)(Cl)Cl)(=[O:26])=[O:25])=[N:17][O:18][N:19]=2)[CH:5]=[CH:6][C:7]=1[F:8].C(O)(=O)C>O1CCCC1.[Zn]>[Br:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[O:12][N:11]=[C:10]2[C:15]2[C:16]([NH:20][CH2:21][CH2:22][NH:23][S:24]([NH2:27])(=[O:25])=[O:26])=[N:17][O:18][N:19]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 118069695HCID 118069695, compound

Product 1

HCID 66605130N-[2-({4-[4-(3-Bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl]sulfamideYield 63.3%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2,2,2-trichloroethyl ({[2-({4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)ethyl]amino}sulfonyl)carbamate (320 mg, 0.50 mmol; from Step Q, Method D) in tetrahydrofuran (THF, 4.0 mL) was stirred at room temperature. Acetic acid (0.30 mL, 5.3 mmol) and zinc flakes (160 mg, 2.5 mmol, 5.0 equiv.) were sequentially added. This reaction mixture was stirred at room temperature for 3 h. HPLC indicated reaction completion. The reaction mixture was filtered through Celite and the Celite was washed with THF. The combined filtrate was concentrated in vacuum and the resulting residue was dissolved in ethyl acetate (20 mL). The ethyl acetate solution was washed with saturated sodium carbonate and brine, dried over sodium sulfate and concentrated. The crude material was crystallized from ethyl acetate and diethyl ether to give the desired product (147 mg, 63%) as an off-white solid.

Workup

  1. customreaction completion
  2. filtrationThe reaction mixture was filtered through Celite
  3. washthe Celite was washed with THF
  4. concentrationThe combined filtrate was concentrated in vacuum
  5. dissolutionthe resulting residue was dissolved in ethyl acetate (20 mL)
  6. washThe ethyl acetate solution was washed with saturated sodium carbonate and brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe crude material was crystallized from ethyl acetate and diethyl ether

Sources & evidence

ORD record
ord-94fcb3b1fc5b49c3b0444bd6c8edda9e
Source dataset
uspto-grants-2016_04
Patent number
US09321755B2

Reaction notes

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