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

HRID 250084ノート

反応式

HRID 250084 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 (1 H, d), 8.06 (1 H, s), 3.96 (1 H, d), 3.66 (1 H, d), 3.20 (1 H, d), 3.08 (1 H, d), 2.87-2.96 (2 H, m), 2.72-2.82 (2 H, m), 2.52 (3 H, s), 2.00-2.19 (2 H, m), 1.51-1.81 (3 H, 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-ceeccbbc307944eca56395ec3969156c
出典データセット
uspto-grants-2011_01
特許番号
US07863291B2

反応ノート

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