Cesium carbonate → HCID 70169281, Verbindung
Reaktionsgleichung
Cl[CH2:2][C@@H:3]([OH:31])[CH2:4][NH:5][C:6]([C:8]1[CH:9]=[N:10][N:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:21][CH:20]([OH:22])[CH2:19][C@@H:18]3[C:23]3[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=3[OH:30])=[N:13][C:12]=12)=[O:7].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[F:29][C:27]1[CH:26]=[CH:25][C:24]2[O:30][CH2:2][C@@H:3]([OH:31])[CH2:4][NH:5][C:6](=[O:7])[C:8]3=[C:12]4[N:13]=[C:14]([CH:15]=[CH:16][N:11]4[N:10]=[CH:9]3)[N:17]3[C@H:18]([CH2:19][C@@H:20]([OH:22])[CH2:21]3)[C:23]=2[CH:28]=1Komponenten
Edukt 2
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 1
Reaktionsbedingungen
- Temperatur
- 85 °C
Versuchsvorschrift
A mixture of N-((S)-3-chloro-2-hydroxypropyl)-5-((R)-2-(5-fluoro-2-hydroxyphenyl)-4-hydroxypyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (0.0407 g, 0.0778 mmol) and Cs2CO3 (0.127 g, 0.389 mmol) in DMF (3.6 mL) was heated at 85° C. for 30 minutes. The reaction mixture was cooled to ambient temperature and filtered. The filtrate was concentrated under reduced pressure to give the crude material which was purified by silica column chromatography, eluting with 0-20% MeOH/EtOAc to afford the crude product. The crude material was purified using chiral column chromatography (Chiral Tech OD-H column, 20% EtOH in hexanes). Isolation of the material having a retention time of about 21.8 minutes afforded the title compound (0.0052 g, 16.2% yield). The stereochemistry of the title compound was confirmed by 1H-NMR nOe experiment. LC/MS (ES+APCI) m/z=414.1 (M+H).
Aufarbeitung
- temperatureThe reaction mixture was cooled to ambient temperature
- filtrationfiltered
- concentrationThe filtrate was concentrated under reduced pressure
- customto give the crude material which
- customwas purified by silica column chromatography
- washeluting with 0-20% MeOH/EtOAc
- customto afford the crude product
- customThe crude material was purified
Quellen und Nachweise
- ORD-Eintrag
- ord-33e093160c4c439cbd02921a921bfec5
- Quelldatensatz
- uspto-grants-2015_01
- Patentnummer
- US08933084B2
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