1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-[4-(5-{3-Chloro-4-[(trifluoromethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]propanoic acid

HRID 423367Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 423367
[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.CC[N:18]=[C:19]=[N:20]CCCN(C)C.C1C=CC2N(O)N=NC=2C=1.ONC(=N)[C:40]1[CH:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[N:45]([CH2:49][CH2:50][C:51]([O:53]CC)=[O:52])[CH:44]=[CH:43]2>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:7][N:20]=[C:19]([C:41]3[CH:40]=[CH:48][CH:47]=[C:46]4[C:42]=3[CH:43]=[CH:44][N:45]4[CH2:49][CH2:50][C:51]([OH:53])=[O:52])[N:18]=2)[CH:8]=[CH:9][C:10]=1[O:11][C:12]([F:15])([F:14])[F:13]

Komponenten

6

Edukt 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 27738453-Chloro-4-(trifluoromethoxy)benzoic acidHCID 178471832ethyl 3-[5-[(Z)-N'-hydroxycarbamimidoyl]indol-1-yl]propanoate

Produkt 1

HCID 249863843-[4-(5-{3-Chloro-4-[(trifluoromethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]propanoic acidAusbeute 25,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

3-Chloro-4-[(trifluoromethyl)oxy]benzoic acid (commercial source) (131 mg), EDCI (114 mg) and HOBT (81 mg) were dissolved in DMF (2.5 ml) and stirred at RT for 10 minutes. Ethyl 3-{5-[(hydroxyamino)(imino)methyl]-1H-indol-1-yl}propanoate (D57) (150 mg) in DMF (2.5 ml) was added and stirring continued at RT for 2 hours. The mixture was then heated at 80° C. overnight. The reaction mixture was evaporated to dryness then extracted with EtOAc (2×25 ml) from H2O (25 ml). The combined organic solutions were evaporated to dryness and the residue treated with EtOH and 2 M aq. NaOH (1:1 mixture, 20 ml). This mixture was stirred at 50° C. for 2 hours then evaporated to remove the EtOH. The resultant precipitate was filtered off and washed with a mixture of H2O and EtOH then 2 M HCl. The residue was recrystallised from hot EtOH to give the title compound (62 mg) as a white solid. δH (d6-DMSO, 400 MHz): 2.81 (2H, t), 4.50 (2H, t), 7.08 (1H, d), 7.36 (1H, apparent t), 7.61 (1H, d), 7.83 (1H, d), 7.89 (1H, d), 7.96 (1H, d), 8.32 (1H, dd), 8.50 (1H, d). MS (ES−): C20H1335CIF3N3O4 requires 451; found 450 (M−H+).

Aufarbeitung

  1. stirringstirring
  2. waitcontinued at RT for 2 hours
  3. temperatureThe mixture was then heated at 80° C. overnight
  4. customThe reaction mixture was evaporated to dryness
  5. extractionthen extracted with EtOAc (2×25 ml) from H2O (25 ml)
  6. customThe combined organic solutions were evaporated to dryness
  7. additionthe residue treated with EtOH and 2 M aq. NaOH (1:1 mixture, 20 ml)
  8. stirringThis mixture was stirred at 50° C. for 2 hours
  9. customthen evaporated
  10. customto remove the EtOH
  11. filtrationThe resultant precipitate was filtered off
  12. washwashed with a mixture of H2O and EtOH
  13. customThe residue was recrystallised from hot EtOH

Quellen und Nachweise

ORD-Eintrag
ord-21e9b576510b4129b9b2060587537c4f
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08101775B2

Notizen zur Reaktion

Wird geladen…