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

HRID 423357Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[OH:11])[C:5]([OH:7])=O.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[Cl:26][C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:36]([NH:38]O)=[NH:37])[CH:34]=2)[N:29]([CH2:40][CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH:28]=1>CN(C=O)C>[Cl:26][C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:36]3[N:37]=[C:5]([C:4]4[CH:8]=[CH:9][C:10]([OH:11])=[C:2]([Cl:1])[CH:3]=4)[O:7][N:38]=3)[CH:34]=2)[N:29]([CH2:40][CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH:28]=1

Participants

Conditions

Temperature: 80 °C

Procedure

3-Chloro-4-hydroxybenzoic acid (commercial) (240 mg, 1.40 mmol) in dry DMF (8 ml) was treated with EDC (292 mg, 1.52 mmol) and HOBt (208 mg, 1.52 mmol) and stirred for 5 minutes. Added ethyl 3-{3-chloro-5-[(hydroxyamino)(imino)methyl]-1H-indol-1-yl}propanoate (D96) (432 mg, 1.40 mmol) and stirred at RT for 30 minutes. The reaction mixture was heated at 80° C. for 7 hours. Added EtOAc (70 ml) and washed with water (70 ml), sat. aq, sodium hydrogen carbonate (70 ml) and water (70 ml). Dried over MgSO4 and evaporated off the solvent. The residue was subjected to chromatography using a biotage (EtOAc/hexane 1:2) to obtain the title compound as 200 mg of white solid. δH (400 MHz, d6-DMSO) 1.10 (3H, t), 2.91 (2H, t), 4.04 (2H, q), 4.50 (2H, t), 7.67-7.70 (2H, m), 7.75 (1H, s), 7.80-7.81 (2H, m), 7.94 (1H, dd), 8.22-8.25 (1H, m), 10.95 (1H, broad s). MS (ES) C21H1735Cl2N3O4 requires 445; found 446 (MH+).

Workup

washAdded EtOAc (70 ml) and washed with water (70 ml)
dry with materialDried over MgSO4
customevaporated off the solvent

Sources & evidence

ORD record: ord-20defe00f96442328a941b6183503f89
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08101775B2

Reaction notes

Loading…