Cesium carbonate → (R)-N-(5-(methylthio)pyrazin-2-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine
Reaktionsgleichung
Cl.Cl.[NH2:3][CH2:4][C@@:5]1([OH:13])[CH:10]2[CH2:11][CH2:12][N:7]([CH2:8][CH2:9]2)[CH2:6]1.C([O-])([O-])=O.[Cs+].[Cs+].[N:20]([C:23]1[CH:28]=[N:27][C:26]([S:29][CH3:30])=[CH:25][N:24]=1)=[C:21]=S.C(N=C=NC(C)C)(C)C>CN(C)C=O>[CH3:30][S:29][C:26]1[N:27]=[CH:28][C:23]([NH:20][C:21]2[O:13][C@:5]3([CH2:4][N:3]=2)[CH:10]2[CH2:9][CH2:8][N:7]([CH2:12][CH2:11]2)[CH2:6]3)=[N:24][CH:25]=1Komponenten
Edukt 4
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 1
Versuchsvorschrift
To (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.375 g, 1.637 mmol) in N,N-dimethylformamide (15 mL) was added Cs2CO3 (1.333 g, 4.09 mmol) and 2-isothiocyanato-5-(methylthio)pyrazine (0.3 g, 1.637 mmol),. The suspension was stirred at room temperature for 30 minutes. N,N′-diisopropylcarbodiimide (0.765 mL, 4.9 mmol) was then added and the mixture was continued to stir at room temperature for 18 hours. The mixture was concentrated and purified by silica gel chromatography (5-25% 9:1 methanol:ammonium hydroxide-ethyl acetate) to afford (R)—N-(5-(methylthio)pyrazin-2-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (0.014 g, 0.04 mmol, 16% yield) as a yellow solid. M.P. 155-60° C. 1H NMR (400 MHz, MeOD) δ ppm 8.13 (1 H, d), 8.06 (1 H, s), 3.96 (1 H, d), 3.66 (1 H, d), 3.20 (1 H, d), 3.08 (1 H, d), 2.87-2.96 (2 H, m), 2.72-2.82 (2 H, m), 2.52 (3 H, s), 2.00-2.19 (2 H, m), 1.51-1.81 (3 H, m). LCMS R.T.=1.01; [M+H]+=306.12.
Aufarbeitung
- stirringto stir at room temperature for 18 hours
- concentrationThe mixture was concentrated
- custompurified by silica gel chromatography (5-25% 9:1 methanol:ammonium hydroxide-ethyl acetate)
Quellen und Nachweise
- ORD-Eintrag
- ord-ceeccbbc307944eca56395ec3969156c
- Quelldatensatz
- uspto-grants-2011_01
- Patentnummer
- US07863291B2
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