Indole-4-carboxylic acid → 3-(3-chloro-4-isopropoxyphenyl)-5-(1H-indol-4-yl)-1,2,4-oxadiazole

HRID 1172933Notes

Reaction equation

HRID 1172933 reaction equation
[NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([C:10]([OH:12])=O)[C:4]=2[CH:3]=[CH:2]1.Cl.CN(C)CCCN=C=NCC.O.N1(O)C2C=CC=CC=2N=N1.[Cl:36][C:37]1[CH:38]=[C:39]([CH:44]=[CH:45][C:46]=1[O:47][CH:48]([CH3:50])[CH3:49])[C:40]([NH:42]O)=[NH:41]>CN(C=O)C.O>[Cl:36][C:37]1[CH:38]=[C:39]([C:40]2[N:42]=[C:10]([C:5]3[CH:6]=[CH:7][CH:8]=[C:9]4[C:4]=3[CH:3]=[CH:2][NH:1]4)[O:12][N:41]=2)[CH:44]=[CH:45][C:46]=1[O:47][CH:48]([CH3:50])[CH3:49]

Participants

7

Reactant 4

HCID 595229Indole-4-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 178458441HCID 178458441, compound

Product 1

HCID 532475423-(3-chloro-4-isopropoxyphenyl)-5-(1H-indol-4-yl)-1,2,4-oxadiazoleYield 35.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

Under an atmosphere of nitrogen a mixture of 1H-indole-4-carboxylic acid (3.88 g, 24.05 mmol), (3-dimethylamino-propyl)-ethyl-carbodiimide hydrochloride (4.61 g, 24.05 mmol) and benzotriazol-1-ol hydrate (3.68 g, 24.05 mmol) in anhydrous DMF (61.4 ml) was stirred at ambient temperature for about 1 h. To the reaction mixture a solution of 3-chloro-N-hydroxy-4-isopropoxybenzamidine (5.0 g, 21.87 mmol) in DMF (11.51 ml) was added. The mixture was stirred and heated at about 140° C. for about 2 h. The mixture was cooled to ambient temperature and poured into water (IL). The product was partitioned between ethyl acetate and the aqueous phase. The organic layer washed with 1N HCl (4×150 mL), 1N NaOH (2×150 mL) and water (2×300 mL), dried over MgSO4 and filtered. The solvent was removed under reduced pressure and the crude product was purified by elution through Florisil with heptane/ethyl acetate (2:1) to give 3-(3-chloro-4-isopropoxyphenyl)-5-(1H-indol-4-yl)-1,2,4-oxadiazole (2.76 g, 35.7%). LCMS (Table 1, Method b) Rt=2.69 min, m/z 354.17 (M+H)+.

Workup

  1. stirringThe mixture was stirred
  2. temperatureheated at about 140° C. for about 2 h
  3. temperatureThe mixture was cooled to ambient temperature
  4. customThe product was partitioned between ethyl acetate
  5. washThe organic layer washed with 1N HCl (4×150 mL), 1N NaOH (2×150 mL) and water (2×300 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customThe solvent was removed under reduced pressure
  9. customthe crude product was purified by elution through Florisil with heptane/ethyl acetate (2:1)

Sources & evidence

ORD record
ord-1bae4205e19e4699911cd9f336867476
Source dataset
uspto-grants-2010_11
Patent number
US07834039B2

Reaction notes

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