反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 120 °C
PROCEDURE
实验过程
Combine 2-(4-bromo-2-fluoro-phenyl)-N-[4-dimethylaminomethyl-5-(1-methyl-cyclopropyl)-thiazol-2-yl]-acetamide (0.45 g, 1.06 mmol), 7-pyridin-4-yl-imidazo[1,2-a]pyridine (0.206 g, 1 equiv.), potassium acetate (0.52 g, 5 equiv.), tetrabutylammonium bromide (0.34 g, 1 equiv.), tris(2,4-di-t-butylphenyl)phosphite (0.034 g, 5 mol %) and NMP (10 mL). De-gas with nitrogen then add palladium (II) acetate (0.012 g, 5 mol %) and place under nitrogen. Heat at 120° C. for 24 hours then let stir at room temperature for an additional day. Dilute with ethyl acetate then wash with water, 1 N NaOH (aq), and aqueous saturated sodium chloride. Dry organics over MgSO4, then filter and concentrate. Purify by reverse phase C18 column HPLC employing a gradient of 5 to 65% to 100% acetonitrile versus 0.03% aqueous HCl then freebase by extraction with ethyl acetate versus 1 N NaOH (aq). Dry the organics over MgSO4, then filter, and concentrate to give product (118 mg tan solid, 21%). MS (ES), m/z 541 (M+1).
WORKUP
后处理
- customDe-gas with nitrogen
- additionDilute with ethyl acetate
- washthen wash with water, 1 N NaOH (aq), and aqueous saturated sodium chloride
- filtrationDry organics over MgSO4, then filter
- concentrationconcentrate
- customPurify by reverse phase C18 column HPLC
- extractionfreebase by extraction with ethyl acetate versus 1 N NaOH (aq)
- dry with materialDry the organics over MgSO4
- filtrationfilter
- concentrationconcentrate