反応式
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]=1参加物
反応物 4
生成物 1
試薬・触媒・溶媒 1
実験手順
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 (1H, s), 7.47 (2H, t), 7.30 (1H, t), 7.16 (2H, d), 6.21 (1H, br. s.), 4.03 (1H, d), 3.72 (1H, d), 3.22 (1H, d), 3.11 (1H, d), 2.73-2.99 (4H, m), 2.00-2.18 (2H, m), 1.54-1.88 (3H, m). LCMS R.T.=1.46; [M+H]+=352.19.
後処理
- 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)
出典と根拠
- ORDレコード
- ord-24109fdf3bbd40a2b27a7939ce63a46c
- 出典データセット
- uspto-grants-2012_11
- 特許番号
- US08309577B2
関連ノート
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