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
- 100 °C
PROCEDURE
实验过程
6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 0.350 g, 0.97 mmol) and (S)-ethyl 6-bromo-1-(1-(2-morpholinoethyl)piperidin-3-yl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 34, 0.480 g, 0.97 mmol) were taken up in dioxane (4 mL), Cs2CO3 (0.633 g, 1.94 mmol) in water (1.000 mL) was added followed by Pd(PPh3)4 (0.112 g, 0.10 mmol). The reaction mixture was heated to 100° C. for 2 h, then 2 ml of 2N LiOH were added and stirred at 100° C. for an additional 30 min. The reaction mixture was cooled to room temperature and solvent evaporated. The resulting residue was taken back up in DMSO (2 ml) and filtered. DMSO solution was purified on an ISCO C18 column using water and acetonitrile. (S)-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-(2-morpholinoethyl)piperidin-3-yl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (0.080 g, 12%) is recovered as a pale yellow solid.
WORKUP
后处理
- temperatureThe reaction mixture was cooled to room temperature
- customsolvent evaporated
- filtrationfiltered
- customDMSO solution was purified on an ISCO C18 column
- custom(S)-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-(2-morpholinoethyl)piperidin-3-yl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (0.080 g, 12%) is recovered as a pale yellow solid