1,2-Dichloroethane → Ethyl 3-[4-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]propanoate

HRID 423340Notes

Reaction equation

HRID 423340 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]([OH:14])=O)[CH:5]=[N:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.O[NH:30][C:31](=[NH:48])[C:32]1[CH:40]=[CH:39][CH:38]=[C:37]2[C:33]=1[CH:34]=[CH:35][N:36]2[CH2:41][CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44]>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:14][N:48]=[C:31]([C:32]3[CH:40]=[CH:39][CH:38]=[C:37]4[C:33]=3[CH:34]=[CH:35][N:36]4[CH2:41][CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])[N:30]=2)[CH:5]=[N:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 180705825-Chloro-6-isopropoxynicotinic acidHCID 178471833HCID 178471833, compound

Product 1

HCID 59318393Ethyl 3-[4-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]propanoateYield 34.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To 5-chloro-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (D61) (1.504 g, 6.97 mmol) in dry DMF (30 ml) was added EDC (1.604 g, 8.37 mmol) and HOBT (1.282 g, 8.37 mmol). Stirred solution at RT for 10 minutes then added ethyl 3-{4-[(hydroxyamino)(imino)methyl]-1H-indol-1-yl}propanoate (N4111-31-A4) (D57) (1.92 g, 6.97 mmol). The mixture was stirred for 30 minutes. LC/MS showed one product (intermediate). The solution was heated at 80° C. for 2 hours. Left standing overnight at RT then heated 80° C. for further 2 hours to give complete reaction. Cooled and added EtOAc (250 ml). The EtOAc was washed with sat. NaHCO3 (150 ml) followed by water (2×200 ml). Dried over MgSO4 and evaporated off the solvent. The residue was subjected to chromatography on the biotage (EtOAc/hexane 1:2). On evaporation of most of the solvent from clean fractions and addition of hexane a white precipitate was formed. The solid was filtered off to obtain 1.1 g of the title product. MS (ES) C23H2335ClN4O4 requires 454; found 455 (MH+).

Workup

  1. waitLeft
  2. waitstanding overnight at RT
  3. temperaturethen heated 80° C. for further 2 hours
  4. customto give complete
  5. customreaction
  6. temperatureCooled
  7. washThe EtOAc was washed with sat. NaHCO3 (150 ml)
  8. dry with materialDried over MgSO4
  9. customevaporated off the solvent
  10. customOn evaporation of most of the solvent
  11. additionfrom clean fractions and addition of hexane a white precipitate
  12. customwas formed
  13. filtrationThe solid was filtered off

Sources & evidence

ORD record
ord-a10c3b25e48348cb8593b8cd05836e38
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

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