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]=[C:27]([O:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:26]=[CH:25][N:24]=1)=[C:21]=S.C(N=C=NC(C)C)(C)C>CN(C)C=O>[O:29]([C:27]1[N:26]=[CH:25][N:24]=[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)[CH:28]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1Komponenten
Edukt 4
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 1
Versuchsvorschrift
To (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.170 g, 0.742 mmol) in N,N-dimethylformamide (20 mL) was added Cs2CO3 (0.604 g, 1.854 mmol) and 4-isothiocyanato-6-phenoxypyrimidine (0.17 g, 0.742 mmol). The suspension was stirred at room temperature for 30 minutes. N,N′-diisopropylcarbodiimide (0.347 mL, 2.225 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-(6-phenoxypyrimidin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (0.21 g, 0.72 mmol, 48.2% yield) as a pale yellow solid. 1H NMR (500 MHz, MeOD) δ ppm 8.43 (1 H, s), 7.47 (2 H, t), 7.30 (1 H, t), 7.16 (2 H, d), 6.21 (1 H, br. s.), 4.03 (1 H, d), 3.72 (1 H, d), 3.22 (1 H, d), 3.11 (1 H, d), 2.73-2.99 (4 H, m), 2.00-2.18 (2 H, m), 1.54-1.88 (3 H, m). LCMS R.T.=1.46; [M+H]+=352.19.
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-f4390104ac6343748b55411ee6a8823e
- Quelldatensatz
- uspto-grants-2011_01
- Patentnummer
- US07863291B2
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