1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-(1H-indol-5-yl)-5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazole

HRID 447901Notes

Reaction equation

HRID 447901 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([C:16]([OH:18])=O)[S:10][C:11]=2[C:12]([F:15])([F:14])[F:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC[N:21]=[C:22]=[N:23]CCCN(C)C.[CH:30]1[CH:31]=[CH:32][C:33]2N(O)N=[N:36][C:34]=2[CH:35]=1.O1CCO[CH2:42][CH2:41]1>>[NH:36]1[C:34]2[C:33](=[CH:32][C:31]([C:22]3[N:23]=[C:16]([C:9]4[S:10][C:11]([C:12]([F:13])([F:14])[F:15])=[C:7]([C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[CH:8]=4)[O:18][N:21]=3)=[CH:30][CH:35]=2)[CH:42]=[CH:41]1

Participants

5

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 312751,4-DioxaneHCID 757711-HydroxybenzotriazoleHCID 27833724-Phenyl-5-(trifluoromethyl)thiophene-2-carboxylic acid

Product 1

HCID 251103463-(1H-indol-5-yl)-5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazoleYield 46.7%

Procedure

To a solution of 4-phenyl-5-(trifluoromethyl)-2-thiophenecarboxylic acid in 1,4-dioxane were added under nitrogen atmosphere EDCI (125 mg, 0.65 mmol) and HOBt (88 mg, 0.65 mmol). The reaction was stirred at room temperature for 30 min followed by addition of N′-hydroxyimidamide (114 mg, 0.65 mmol), the reaction was stirred for 30 additional minutes at room temperature followed by 16 h at 95° C. The reaction was concentrated under reduced pressure. The crude was diluted with EtOAc (80 mL) and washed with a saturated solution of NaHCO3 (2×50 ml). The organic phase was dried over Na2SO4 anhydrous and concentrated under reduced pressure. The product was purified by column chromatography using CH2Cl2:MeOH (9:1) to yield 91 mg (46.7%) of the product. MS (EI) m/z: 412 (M+).

Workup

  1. stirringthe reaction was stirred for 30 additional minutes at room temperature
  2. waitfollowed by 16 h at 95° C
  3. concentrationThe reaction was concentrated under reduced pressure
  4. additionThe crude was diluted with EtOAc (80 mL)
  5. washwashed with a saturated solution of NaHCO3 (2×50 ml)
  6. dry with materialThe organic phase was dried over Na2SO4 anhydrous
  7. concentrationconcentrated under reduced pressure
  8. customThe product was purified by column chromatography

Sources & evidence

ORD record
ord-3d6dd430590d4c8babf9a29031272426
Source dataset
uspto-grants-2013_07
Patent number
US08481573B2

Reaction notes

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