1-Hydroxybenzotriazole → N-biphenyl-4-yl-3-[4-(2-bromo-5-fluoro-benzoyl)-piperazin-1-yl]-3-oxo-propionamide
Reaktionsgleichung
C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[Br:20][C:21]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:22]=1[C:23]([OH:25])=O.CCN=C=NCCCN(C)C.Cl.Cl.[C:44]1([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[CH:49]=[CH:48][C:47]([NH:50][C:51](=[O:61])[CH2:52][C:53](=[O:60])[N:54]2[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]2)=[CH:46][CH:45]=1>CN(C=O)C.O>[C:44]1([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[CH:45]=[CH:46][C:47]([NH:50][C:51](=[O:61])[CH2:52][C:53]([N:54]2[CH2:55][CH2:56][N:57]([C:23](=[O:25])[C:22]3[CH:26]=[C:27]([F:30])[CH:28]=[CH:29][C:21]=3[Br:20])[CH2:58][CH2:59]2)=[O:60])=[CH:48][CH:49]=1Komponenten
Edukt 5
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 2
Reaktionsbedingungen
- Temperatur
- 10 °C
Versuchsvorschrift
HOBt (34 mg, 0.25 mmol) and DIPEA (67.9 mg, 0.51 mmol) were added to a stirred solution of 2-bromo-5-fluorobenzoic acid (46 mg, 0.21 mmol) in DMF (2 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (48 mg, 0.25 mmol) followed by N-biphenyl-4-yl-3-oxo-3-piperazin-1-yl-propionamide hydrochloride (75 mg, 0.2 mmol) were added. The reaction mixture was stirred at room temperature overnight, then diluted with water. The resulting precipitate was filtered, then purified by column chromatography using silica gel 60-120 mesh (80% ethyl acetate in hexane) to afford 40 mg (37%) of N-biphenyl-4-yl-3-[4-(2-bromo-5-fluoro-benzoyl)-piperazin-1-yl]-3-oxo-propionamide. LCMS: 524.09 (M+1)+, 96%. 1H NMR: (CDCl3): δ 9.6 (d, 1H), 7.6 (m, 7H), 7.42 (t, 2H), 7.34 (t, 1H), 7.0 (m, 2H), 3.96 (m, 2H), 3.7 (m, 4H), 3.5 (d, 2H), 3.3 (m, 2H).
Aufarbeitung
- additionwere added
- filtrationThe resulting precipitate was filtered
- custompurified by column chromatography
Quellen und Nachweise
- ORD-Eintrag
- ord-08b3c15d381041fcbb8f6e7fbb205e25
- Quelldatensatz
- uspto-grants-2011_10
- Patentnummer
- US08039463B2
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