Ethyl (chloroformyl)acetate → Ethyl 6,8-dichloroimidazo[1,2-b]pyridazine-3-carboxylate
反応式
[Cl:1]C(C=O)C(OCC)=O.BrC1C=C(Cl)N=NC=1N.Br[C:20]1[C:21]2[N:22]([C:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:28][N:29]=2)[N:23]=[C:24]([Cl:26])[CH:25]=1>>[Cl:26][C:24]1[CH:25]=[C:20]([Cl:1])[C:21]2[N:22]([C:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:28][N:29]=2)[N:23]=1参加物
反応条件
- 温度
- 90 °C
実験手順
To a 250 mL round-bottomed flask was added ethyl 2-chloro-3-oxopropanoate (4.33 g, 28.8 mmol) and 4-bromo-6-chloropyridazin-3-amine (5 g, 23.99 mmol). The solution was heated to 90° C. for 16 hours. The solution was quenched with ethyl acetate and washed with water. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude material was purified by ISCO (10% ethyl acetate/dichloromethane; 80 g column) to give a mixture of ethyl 8-bromo-6-chloroimidazo[1,2-b]pyridazine-3-carboxylate and ethyl 6,8-dichloroimidazo[1,2-b]pyridazine-3-carboxylate (2.1 g, 29% yield). LC/MS, m/z 256.96 (M+1). HPLC Rt, 2.54 min. LC/MS, m/z 303.92 (M+1). HPLC Rt, 2.63 min. Waters Sunfire C18 column (4.6×50 mm) 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.
後処理
- customThe solution was quenched with ethyl acetate
- washwashed with water
- dry with materialThe organic layer was dried over anhydrous sodium sulfate
- concentrationconcentrated in vacuo
- customThe crude material was purified by ISCO (10% ethyl acetate/dichloromethane; 80 g column)
- customto give
出典と根拠
- ORDレコード
- ord-ee428c6a52754a0fb7cf030865aa817b
- 出典データセット
- uspto-grants-2013_03
- 特許番号
- US08389527B2
反応ノート
読み込み中…