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+].[N:20]([C:23]1[CH:28]=[C:27]([C:29]2[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=2)[N:26]=[CH:25][N:24]=1)=[C:21]=S.C(N=C=NC(C)C)(C)C>CN(C)C=O>[N:32]1[CH:31]=[CH:30][C:29]([C:27]2[N:26]=[CH:25][N:24]=[C:23]([NH:20][C:21]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:28]=2)=[CH:34][CH:33]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.059 g, 0.257 mmol) in N,N-dimethylformamide (15 mL) was added Cs2CO3 (0.209 g, 0.642 mmol) and 4-isothiocyanato-6-(pyridin-4-yl)pyrimidine (0.055 g, 0.257 mmol). The suspension was stirred at room temperature for 30 minutes. N,N′-diisopropylcarbodiimide (0.12 mL, 0.77 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 (0-10% [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 (0.014 g, 0.04 mmol, 16% yield) as a yellow film. 1H NMR (400 MHz, MeOD) δ ppm 8.85 (1 H, d), 8.67 (2 H, dd), 8.04 (2 H, dd), 7.34 (1 H, br. s.), 4.06 (1 H, d), 3.76 (1 H, d), 3.23 (1 H, d), 3.10 (1 H, d), 2.70-2.99 (4 H, m), 2.01-2.22 (2 H, m), 1.53-1.86 (3 H, m). LCMS R.T.=0.42; [M+H]+=337.14.
Workup
- stirringto stir at room temperature for 18 hours
- concentrationThe mixture was concentrated
- custompurified by silica gel chromatography (0-10% [9:1 methanol:ammonium hydroxide]-ethyl acetate)
Sources & evidence
- ORD record
- ord-46cc329057e0419e871f09dcbbd366b3
- Source dataset
- uspto-grants-2011_01
- Patent number
- US07863291B2
Reaction notes
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