Cesium carbonate → (R)-N-(5-(methylthio)pyrazin-2-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine

HRID 1875949ノート

反応式

HRID 1875949 の反応式
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]=[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]=1

参加物

6

反応物 4

HCID 10796Cesium carbonateHCID 12734DiisopropylcarbodiimideHCID 574765802-Isothiocyanato-5-(methylthio)pyrazineHCID 66724709(S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride

生成物 1

HCID 58087960(R)-N-(5-(methylthio)pyrazin-2-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine収率 16%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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 (1H, d), 8.06 (1H, s), 3.96 (1H, d), 3.66 (1H, d), 3.20 (1H, d), 3.08 (1H, d), 2.87-2.96 (2H, m), 2.72-2.82 (2H, m), 2.52 (3H, s), 2.00-2.19 (2H, m), 1.51-1.81 (3H, m). LCMS R.T.=1.01; [M+H]+=306.12.

後処理

  1. stirringto stir at room temperature for 18 hours
  2. concentrationThe mixture was concentrated
  3. 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-1842b38861aa4328bdfc04316b1ea5c6
出典データセット
uspto-grants-2012_11
特許番号
US08309577B2

反応ノート

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