Diisopropylethylamine → 2-bromo-6-[(1S)-1-(3-fluorobenzyl)-2-hydroxyethyl]-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one
Reaktionsgleichung
[Br:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8]CC)=O)=[C:4]([CH2:13]Br)[N:3]=1.[NH2:15][C@@H:16]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=1)[CH2:17][OH:18].C(N(CC)C(C)C)(C)C.C([O-])(O)=O.[Na+]>CCOC(C)=O.O1CCOCC1>[Br:1][C:2]1[N:3]=[C:4]2[CH2:13][N:15]([C@@H:16]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)[CH2:17][OH:18])[C:6](=[O:8])[C:5]2=[CH:11][CH:12]=1Komponenten
7
Edukt 4
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 2
Reaktionsbedingungen
- Temperatur
- 67 °C
Versuchsvorschrift
Ethyl 6-bromo-2-(bromomethyl)nicotinate (0.17 g, 0.53 mmol), (2S)-2-amino-3-(3-fluorophenyl)propan-1-ol (0.11 g, 0.64 mmol), N,N-diisopropylethylamine (0.2 g, 2 mmol) and 1,4-dioxane (5 mL) were mixed in one 20 mL microwave tube, and the mixture was stirred at 67° C. for overnight. LC-MS showed most starting material was converted to Br-replacement product. Then the temperature was raised to 125° C. for 45 mins, cooled to room temperature, then worked up with EtOAc and aqueous NaHCO3 solution, extracted twice with EtOAc and dried over sodium sulfate, and concentrated under reduced pressure. Purification by combi-flash chromatography gave the desired product. LC-MS found: 365.1 (M+H)+.
Aufarbeitung
- temperatureThen the temperature was raised to 125° C. for 45 mins
- temperaturecooled to room temperature
- extractionextracted twice with EtOAc
- dry with materialdried over sodium sulfate
- concentrationconcentrated under reduced pressure
- customPurification by combi-flash chromatography
Quellen und Nachweise
- ORD-Eintrag
- ord-08054d47a9b94fecbdcead17394ab71f
- Quelldatensatz
- uspto-grants-2014_11
- Patentnummer
- US08895571B2
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