反応式
[NH2:1][C:2]1[C:3]([C:10]([NH:12][C:13](SC)=[NH:14])=[O:11])=[N:4][C:5]([Cl:9])=[C:6]([NH2:8])[N:7]=1.C(OC([N:24]1[CH2:29][CH2:28][CH2:27][C@H:26]([NH2:30])[CH2:25]1)=O)(C)(C)C.C(N(CC)CC)C>CN(C=O)C.C(O)(C)C>[NH2:1][C:2]1[C:3]([C:10]([NH:12][C:13]([NH:30][CH:26]2[CH2:27][CH2:28][CH2:29][NH:24][CH2:25]2)=[NH:14])=[O:11])=[N:4][C:5]([Cl:9])=[C:6]([NH2:8])[N:7]=1参加物
反応物 3
生成物 1
試薬・触媒・溶媒 1
反応条件
- 温度
- 70 °C
実験手順
A mixture of 1.17 g (4.5 mmol) 4-Aminomethyl-4-phenethyl-piperidine-1-carbocylic acid tert-butyl ester (intermediate 3), 1 mg (4.9 mmol) (S)-3-amino-piperidine-1-carboxylic acid tert-butyl ester and 125 μl triethylamin in 50 ml DMF/iso-propanol (1:3) is stirred at 70° C. overnight. Then the reaction mixture is concentrated under reduced pressure. Then 50 ml 25% TFA in dicholoromethane is added and the mixture is stirred for 2 h at room temperature and evaporated. The residue is treated with excess HCl in methanol and evaporated again to yield 430 mg N-(3,5-Diamino-6-chloro-pyrazine-2-carbonyl)-N′-piperidin-3-yl-guanidine. Step B: 100 mg N-(3,5-Diamino-6-chloro-pyrazine-2-carbonyl)-N′-piperidin-3-yl-guanidine, 125 μl triethylamine and 62 mg 3-bromomethyl-benzoic acid methyl ester in 3 ml DMF were stirred at room temperature for 6 h. Then the reaction mixture is concentrated under reduced pressure and the residue is purified by preparative reverse phase HPLC (gradient of acetonitrile and water+0.2% trifluoroacetic acid, 25° C.). Fractions containing the title compound were concentrated under reduced pressure.
後処理
- concentrationThen the reaction mixture is concentrated under reduced pressure
- additionThen 50 ml 25% TFA in dicholoromethane is added
- stirringthe mixture is stirred for 2 h at room temperature
- customevaporated
- additionThe residue is treated with excess HCl in methanol
- customevaporated again
出典と根拠
- ORDレコード
- ord-ecf49f648d6e427da2a929476b212b84
- 出典データセット
- uspto-grants-2014_09
- 特許番号
- US08841309B2
関連ノート
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