Dimethylacetamide → 4-(5-chloropyridin-3-yl)-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[4-(trifluoromethyl)benzyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile
Reaktionsgleichung
C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[C:48]1[N:53]=[C:52]([C:54]2[CH:55]=[N:56][CH:57]=[C:58]([Cl:60])[CH:59]=2)[C:51]2[N:61]([CH2:73][C:74]3[CH:79]=[CH:78][C:77]([C:80]([F:83])([F:82])[F:81])=[CH:76][CH:75]=3)[C:62]([N:64]3[CH2:69][CH2:68][O:67][C@@H:66]4[CH2:70][CH2:71][CH2:72][C@@H:65]34)=[N:63][C:50]=2[CH:49]=1.[CH3:84][N:85](C)C(=O)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[C-]#N.[Zn+2].[C-]#N.[Zn]>[Cl:60][C:58]1[CH:59]=[C:54]([C:52]2[C:51]3[N:61]([CH2:73][C:74]4[CH:75]=[CH:76][C:77]([C:80]([F:83])([F:81])[F:82])=[CH:78][CH:79]=4)[C:62]([N:64]4[CH2:69][CH2:68][O:67][C@@H:66]5[CH2:70][CH2:71][CH2:72][C@@H:65]45)=[N:63][C:50]=3[CH:49]=[C:48]([C:84]#[N:85])[N:53]=2)[CH:55]=[N:56][CH:57]=1Komponenten
Edukt 3
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 3
Reaktionsbedingungen
- Temperatur
- 80 °C
Versuchsvorschrift
Palladium(II) acetate (70 mg, 0.312 mmol) and (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (195 mg, 0.313 mmol) were placed in a dry flask. N,N-dimethylacetamide (18.7 mL) was added and the mixture was degassed for three minutes with nitrogen. Sulfuric acid (0.015 mL) was added, and the mixture was degassed for an additional three minutes with nitrogen. The flask was sealed and heated to 80° C. for 30 minutes. The mixture was cooled to room temperature and added to a separate nitrogen purged flask containing 6-chloro-4-(5-chloropyridin-3-yl)-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[4-(trifluoromethyl)benzyl]-3H-imidazo[4,5-c]pyridine (racemic; 0.5 g, 0.9 mmol), zinc cyanide (46 mg, 0.45 mmol), and zinc (6 mg, 0.09 mmol). The flask was purged with nitrogen for five minutes, sealed, and heated to 100° C. for 2 hrs. The reaction mixture was cooled to room temperature, filtered, diluted with ethyl acetate, and washed with water and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to afford 4-(5-chloropyridin-3-yl)-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[4-(trifluoromethyl)benzyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (racemic). MS APCl calc'd. for C27H22ClF3N6O [M+H]+ 539. found 539.
Aufarbeitung
- customthe mixture was degassed for three minutes with nitrogen
- additionSulfuric acid (0.015 mL) was added
- customthe mixture was degassed for an additional three minutes with nitrogen
- customThe flask was sealed
- temperatureThe mixture was cooled to room temperature
- additionadded to a separate nitrogen purged flask
- customThe flask was purged with nitrogen for five minutes
- customsealed
- temperatureheated to 100° C. for 2 hrs
- temperatureThe reaction mixture was cooled to room temperature
- filtrationfiltered
- additiondiluted with ethyl acetate
- washwashed with water and brine
- dry with materialThe organic layer was dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)
Quellen und Nachweise
- ORD-Eintrag
- ord-765b3ae8f07d4c23ae78eebea257900d
- Quelldatensatz
- uspto-grants-2014_09
- Patentnummer
- US08846657B2
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