1-Hydroxybenzotriazole → 5-Phenyl-[1,3,4]oxadiazole-2-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide

HRID 1178105Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1178105
CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.OC(C(F)(F)F)=O.[NH2:39][CH2:40][C:41]([N:43]1[CH2:48][CH2:47][N:46]([C:49](=[O:60])[C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=2[C:56]([F:59])([F:58])[F:57])[CH2:45][CH2:44]1)=[O:42].[Li+].[C:62]1([C:68]2[O:72][C:71]([C:73]([O-])=[O:74])=[N:70][N:69]=2)[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1>CN(C=O)C.O>[O:42]=[C:41]([N:43]1[CH2:44][CH2:45][N:46]([C:49](=[O:60])[C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=2[C:56]([F:59])([F:57])[F:58])[CH2:47][CH2:48]1)[CH2:40][NH:39][C:73]([C:71]1[O:72][C:68]([C:62]2[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=2)=[N:69][N:70]=1)=[O:74]

Komponenten

8

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 669534535-Phenyl-[1,3,4]oxadiazole-2-carboxylic acid lithium saltHCID 866340882-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt

Produkt 1

HCID 578556405-Phenyl-[1,3,4]oxadiazole-2-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amideAusbeute 22,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

DIPEA (106 mg, 0.142 mL, 0.82 mmol) followed by HOBT (40.8 mg, 0.30 mmol), EDCI.HCl (131.8 mg, 0.69 mmol) and 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt (129 mg, 0.3 mmol) were added sequentially to a stirred solution of 5-phenyl-[1,3,4]oxadiazole-2-carboxylic acid lithium salt (52 mg, 0.27 mmol) in DMF (5 mL). The resulting mixture was maintained at room temperature for 6 hrs. Cold water was added and the product was extracted with ethyl acetate. The organic layer was washed with saturated brine solution, dried over sodium sulphate and concentrated. The crude residue was purified by column chromatography (using 60-120 mesh silica gel and 50% EtOAc in hexane as eluent) to afford 30 mg (22.4% yield) of 5-phenyl-[1,3,4]oxadiazole-2-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide as a white solid, LCMS purity: 87.99%, 1H NMR: (DMSO) δ 9.2 (t, 1H), 8.1 (d, 2H), 7.9-7.72 (dd, 2H), 7.72-7.6 (m, 3H), 7.6-7.5 (t, 1H), 4.3-4.1 (dd, 2H), 3.8-3.5 (m, 4H), 3.3-3.0 (m, 4H).

Aufarbeitung

  1. extractionthe product was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine solution
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated
  5. customThe crude residue was purified by column chromatography (using 60-120 mesh silica gel and 50% EtOAc in hexane as eluent)

Quellen und Nachweise

ORD-Eintrag
ord-ebeec8d430784e1a908ecf2e8124de65
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07842696B2

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