Potassium Carbonate → 4-(4-bromo-5-chloro-2-fluorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one
Reaktionsgleichung
[Br:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([NH:9][C:10]([NH:12][NH:13][C:14](=O)[CH2:15][C@@H:16]2[CH2:20][CH2:19][N:18]([C:21]([CH:23]3[CH2:25][CH2:24]3)=[O:22])[CH2:17]2)=[O:11])=[C:4]([F:27])[CH:3]=1.C([O-])([O-])=O.[K+].[K+]>O>[Br:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([N:9]2[C:14]([CH2:15][C@@H:16]3[CH2:20][CH2:19][N:18]([C:21]([CH:23]4[CH2:25][CH2:24]4)=[O:22])[CH2:17]3)=[N:13][NH:12][C:10]2=[O:11])=[C:4]([F:27])[CH:3]=1Komponenten
Edukt 2
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 1
Reaktionsbedingungen
- Temperatur
- 115 °C
Versuchsvorschrift
N-(4-bromo-5-chloro-2-fluorophenyl)-2-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]acetyl}hydrazinecarboxamide (2.426 mmol) and K2CO3 (8.49 mmol) were added to a round-bottom flask and suspended in water (105 mL). The mixture was heated at reflux (115° C.) for 21 h. Analysis by LCMS indicated formation of desired product (and other major by-products). The reaction was cooled to room temperature and the pH was adjusted to ˜6 with 1N aq HCl and poured into a separatory funnel containing ethyl acetate. The aqueous layer was extracted with ethyl acetate (3×) and the combined organic layers were dried over Na2SO4, filtered, and concentrated to an oil. The residue was purified by silica gel chromatography (0-30% isopropanol/ethyl acetate). The desired fractions were combined and concentrated to afford the title product as an off-white solid (401 mg, 38%). MS(ES)+ m/e 443.0, 445.0 [M+H]+.
Aufarbeitung
- temperatureThe mixture was heated
Quellen und Nachweise
- ORD-Eintrag
- ord-bc05d8a53e9f4ce598f5a0e8798bcdc6
- Quelldatensatz
- uspto-grants-2016_05
- Patentnummer
- US09340529B2
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