1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-[4-(5-{5-Chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]propanoic acid

HRID 423369

Reaktionsgleichung

Reaktionsgleichung von HRID 423369
[OH:1][NH:2][C:3](=[NH:20])[C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[CH:7][N:8]2[CH2:13][CH2:14][C:15]([O:17]CC)=[O:16].[Cl:21][C:22]1[CH:23]=[C:24]([C:32](O)=O)[CH:25]=[N:26][C:27]=1[O:28][CH:29]([CH3:31])[CH3:30].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C>[Cl:21][C:22]1[CH:23]=[C:24]([C:32]2[O:1][N:2]=[C:3]([C:4]3[CH:12]=[CH:11][CH:10]=[C:9]4[C:5]=3[CH:6]=[CH:7][N:8]4[CH2:13][CH2:14][C:15]([OH:17])=[O:16])[N:20]=2)[CH:25]=[N:26][C:27]=1[O:28][CH:29]([CH3:30])[CH3:31]

Komponenten

6

Edukt 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 180705825-Chloro-6-isopropoxynicotinic acidHCID 178471833HCID 178471833, Verbindung

Produkt 1

HCID 249867423-[4-(5-{5-Chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]propanoic acidAusbeute 20,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Ethyl 3-{4-[(hydroxyamino)(imino)methyl]-1H-indol-1-yl}propanoate (D57) (150 mg) in DMF (2.5 ml) was added to a solution of 5-chloro-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (D61) (118 mg), HOBT (81 mg) and EDCI (114 mg) which had been stirring at RT for 10 minutes in DMF (2.5 ml). The resultant mixture was stirred at RT for 2 hours then heated at 80° C. for three days. The reaction mixture was evaporated to dryness and extracted from H2O (25 ml) with EtOAc (2×25 ml). The combined organics were evaporated and the residue stirred in EtOH/2 M aq. NaOH (1:1 mixture, 20 ml) at 50° C. for 2 hours. The EtOH was evaporated and the precipitate removed by filtration. This was acidified then purified by MDAP to give the title compound (48 mg) as an off white solid. δH (d6-DMSO, 400 MHz): 1.40 (6H, d), 2.80 (2H, t), 4.50 (2H, t), 5.46 (1H, septet), 7.08 (1H, d), 7.36 (1H, apparent t), 7.60 (1H, d), 7.82 (1H, d), 7.95 (1H, d), 8.60 (1H, d), 8.97 (1H, d). MS (ES−): C21H1935ClN4O4 requires 426; found 425 (M−H+).

Aufarbeitung

  1. customThe reaction mixture was evaporated to dryness
  2. extractionextracted from H2O (25 ml) with EtOAc (2×25 ml)
  3. customThe combined organics were evaporated
  4. customThe EtOH was evaporated
  5. customthe precipitate removed by filtration
  6. customThis was acidified then purified by MDAP

Quellen und Nachweise

ORD-Eintrag
ord-6f9cec4545a74e8c8c10ac344dbdde35
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08101775B2

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