Cesium carbonate → (R)-N-(6-(pyridin-4-yl)pyrimidin-4-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine
Reaction equation
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+].ClC1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[C:31]([N:33]=[C:34]=S)[N:30]=[CH:29][N:28]=2)=[CH:23][CH:22]=1.C([N:39]=C=NC(C)C)(C)C>CN(C)C=O>[N:39]1[CH:26]=[CH:25][C:24]([C:27]2[N:28]=[CH:29][N:30]=[C:31]([NH:33][C:34]3[O:13][C@:5]4([CH2:4][N:3]=3)[CH:10]3[CH2:9][CH2:8][N:7]([CH2:12][CH2:11]3)[CH2:6]4)[CH:32]=2)=[CH:23][CH:22]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.298 g, 1.300 mmol) in N,N-dimethylformamide (15 mL) was added Cs2CO3 (1.059 g, 3.25 mmol) and 4-(4-chlorophenyl)-6-isothiocyanatopyrimidine (0.322 g, 1.300 mmol). The suspension was stirred at room temperature for 30 minutes. N,N′-Diisopropylcarbodiimide (0.608 mL, 3.90 mmol) was then added and the mixture was stirred 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-(pyridin-4-yl)pyrimidin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (0.104 g, 0.276 mmol, 21% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 9.54 (1 H, br. s.), 8.83 (1 H, d), 7.89-8.04 (2 H, m), 7.41-7.54 (2 H, m), 7.33 (1 H, br. s.), 4.02 (1 H, d), 3.71 (1 H, d), 3.42 (1 H, d), 2.73-3.15 (5 H, m), 2.10-2.31 (2 H, m), 1.46-1.89 (3 H, m). LCMS R.T.=1.92; [M]+=370.35.
Workup
- stirringthe mixture was stirred at room temperature for 18 hours
- concentrationThe mixture was concentrated
- custompurified by silica gel chromatography (5-25% 9:1 methanol:ammonium hydroxide-ethyl acetate)
Sources & evidence
- ORD record
- ord-deb0adb95ebe461d827d26a45fc6a0a2
- Source dataset
- uspto-grants-2011_01
- Patent number
- US07863291B2
Reaction notes
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