Diisopropylcarbodiimide → HCID 59214275, compound

HRID 552846Notes

Reaction equation

HRID 552846 reaction equation
[F:1][C:2]([F:21])([F:20])[C:3]([CH3:19])([CH3:18])[O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][C:6]=1[C:14]([F:17])([F:16])[F:15].[NH2:22][C:23](=[N:37]O)[C:24]1[CH:32]=[CH:31][CH:30]=[C:29]2[C:25]=1[CH:26]=[CH:27][N:28]2[CH2:33][C:34]([NH2:36])=[O:35].CC(C)N=C=NC(C)C>O1CCOCC1>[F:20][C:2]([F:1])([F:21])[C:3]([CH3:18])([CH3:19])[O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]2[O:11][N:37]=[C:23]([C:24]3[CH:32]=[CH:31][CH:30]=[C:29]4[C:25]=3[CH:26]=[CH:27][N:28]4[CH2:33][C:34]([NH2:36])=[O:35])[N:22]=2)=[CH:7][C:6]=1[C:14]([F:16])([F:15])[F:17]

Participants

5

Reactant 3

HCID 12734DiisopropylcarbodiimideHCID 59214395HCID 59214395, compoundHCID 72532776HCID 72532776, compound

Product 1

HCID 59214275HCID 59214275, compoundYield 20.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 4-(2,2,2-trifluoro-1,1-dimethylethoxy)-3-(trifluoromethyl)benzoic acid (118 mg) and 2-{4-[amino(hydroxyimino)methyl]-1H-indol-1-yl}acetamide (104 mg) in dioxane (5 ml) was added DIC (69 μl), followed by stirring at room temperature for 3 hours, and then heating under reflux for 20 hours. The reaction solution was concentrated, and then to the residue was added water (15 ml), followed by extraction with chloroform (15 ml). The organic layer was washed with a saturated aqueous NaHCO3 solution and saturated brine, dried over anhydrous MgSO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC (column: CAPCEL PAK, C18, MG, S-5, 30×50 mm; solvent: 50-90% acetonitrile/10 mM ammonium carbonate-ammonia (pH 9.2); 40 ml/min), and crystallized with diisopropyl ether to obtain 2-(4{5-[4-(2,2,2-trifluoro-1,1-dimethylethoxy)-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetamide (40 mg) as a white solid.

Workup

  1. temperatureheating
  2. temperatureunder reflux for 20 hours
  3. concentrationThe reaction solution was concentrated
  4. additionto the residue was added water (15 ml)
  5. extractionfollowed by extraction with chloroform (15 ml)
  6. washThe organic layer was washed with a saturated aqueous NaHCO3 solution and saturated brine
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by preparative HPLC (column: CAPCEL PAK, C18, MG, S-5, 30×50 mm; solvent: 50-90% acetonitrile/10 mM ammonium carbonate-ammonia (pH 9.2); 40 ml/min)
  11. customcrystallized with diisopropyl ether

Sources & evidence

ORD record
ord-ea0f04eb8e564ea380efef1edbda42c4
Source dataset
uspto-grants-2011_05
Patent number
US07951825B2

Reaction notes

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