1,2-Dichloroethane → Ethyl 3-[3-chloro-5-(5-{3-chloro-4-[(trifluoromethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]propanoate

HRID 423350Notes

Reaction equation

HRID 423350 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][C:12]([F:15])([F:14])[F:13])[C:5]([OH:7])=O.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[Cl:30][C:31]1[C:39]2[C:34](=[CH:35][CH:36]=[C:37]([C:40]([NH:42]O)=[NH:41])[CH:38]=2)[N:33]([CH2:44][CH2:45][C:46]([O:48][CH2:49][CH3:50])=[O:47])[CH:32]=1>CN(C=O)C>[Cl:30][C:31]1[C:39]2[C:34](=[CH:35][CH:36]=[C:37]([C:40]3[N:41]=[C:5]([C:4]4[CH:8]=[CH:9][C:10]([O:11][C:12]([F:15])([F:14])[F:13])=[C:2]([Cl:1])[CH:3]=4)[O:7][N:42]=3)[CH:38]=2)[N:33]([CH2:44][CH2:45][C:46]([O:48][CH2:49][CH3:50])=[O:47])[CH:32]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 27738453-Chloro-4-(trifluoromethoxy)benzoic acidHCID 178471837ethyl 3-[3-chloro-5-[(Z)-N'-hydroxycarbamimidoyl]indol-1-yl]propanoate

Product 1

HCID 59318427Ethyl 3-[3-chloro-5-(5-{3-chloro-4-[(trifluoromethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]propanoateYield 55.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

3-Chloro-4-[(trifluoromethyl)oxy]benzoic acid (commercial: ABCR) (168 mg, 0.70 mmol) stirring in DMF (6 ml) was treated with EDC (146 mg, 0.76 mmol) followed by HOBt (104 mg, 0.76 mmol). The resultant solution was stirred for 15 minutes. Added ethyl 3-{3-chloro-5-[(hydroxyamino)(imino)methyl]-1H-indol-1-yl}propanoate (D96) (216 mg, 0.70 mmol) and stirred at RT for 45 minutes. The solution was heated at 80° C. for 6 hours then left standing at room temperature overnight. Single product formed by LC/MS. Added EtOAc (50 ml) and washed with water (50 ml), saturated aqueous sodium hydrogen carbonate (50 ml) and water (50 ml). Dried over MgSO4 and evaporated off the solvent. The residue was crystallised from ethanol to yield 200 mg of white solid. δH (400 MHz, d6-DMSO) 1.11 (3H, t), 2.92 (2H, t), 4.00 (2H, q), 4.49 (2H, t), 7.75 (1H, s), 7.80 (1H, d), 7.85 (1H, dd), 7.95 (1H, dd) 8.23 (1H, d) 8.30 (1H, dd), 8.47 (1H, d). MS (ES) C22H1635Cl37ClF3N3O4 requires 515; found 516 (MH+).

Workup

  1. waitthen left
  2. customSingle product formed by LC/MS
  3. washAdded EtOAc (50 ml) and washed with water (50 ml), saturated aqueous sodium hydrogen carbonate (50 ml) and water (50 ml)
  4. dry with materialDried over MgSO4
  5. customevaporated off the solvent
  6. customThe residue was crystallised from ethanol

Sources & evidence

ORD record
ord-05322069696d40c8a186404dbdaa74e8
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

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