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
- 110 °C
PROCEDURE
实验过程
In a 25 ml round bottom flask containing 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate (563 mg, 683 μmol, Eq: 1.4), (6-(6-chloroquinolin-8-ylamino)pyridin-3-yl)(morpholino)methanone (180 mg, 488 μmol, Eq: 1.00), X-PHOS (34.9 mg, 73.2 μmol) and potassium phosphate (228 mg, 1.07 mmol) was added BuOH (7 mL) and H2O (1.65 mL). The flask was evacuated and backfilled with argon before addition of Pd(dba)2 (19.6 mg, 34.2 μmol). The flask was evacuated and backfilled with argon again and heated at 110° C. for 2.5 hrs. LC/MS showed the presence of desired product as a mixture with 6-tert-butyl-8-fluoro-2-(2-hydroxymethyl-3-{8-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-quinolin-6-yl}-phenyl)-2H-phthalazin-1-one. The reaction mixture was cooled to ambient temperature, diluted with 35 ml water and 35 ml EtOAc and shaken. The EtOAc phase was collected and washed with an equal volume of brine. The aqueous phase was back-extracted with 2×30 ml EtOAc. The combined organic extract was dried (MgSO4), and concentrated in vacuo. The crude product was purified by preparative thin layer chromatography (3 plates), eluting with 2% methanol/methylene chloride to provide the desired product (together with some 6-tert-butyl-8-fluoro-2-(2-hydroxymethyl-3-{8-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-quinolin-6-yl}-phenyl)-2H-phthalazin-1-one) as a light brown foamy solid (310 mg).
WORKUP
后处理
- customThe flask was evacuated
- customThe flask was evacuated
- temperatureThe reaction mixture was cooled to ambient temperature
- additiondiluted with 35 ml water and 35 ml EtOAc
- customThe EtOAc phase was collected
- washwashed with an equal volume of brine
- extractionThe aqueous phase was back-extracted with 2×30 ml EtOAc
- extractionThe combined organic extract
- dry with materialwas dried (MgSO4)
- concentrationconcentrated in vacuo
- customThe crude product was purified by preparative thin layer chromatography (3 plates)
- washeluting with 2% methanol/methylene chloride