反应详情

温度

80 °C

Into a reaction tube were placed CsF (1.0 g, 6.5 mmol, 2.5 equiv), CuI (50 mg, 0.26 mmol, 0.1 equiv), 1-chloro-4-iodo-benzene (740 mg, 3.12 mmol, 1.2 equiv), (2,4-dimethoxy-benzyl)-(2-oxo-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-yl)-carbamic acid tert-butyl ester (Example 20, product from Step 4) (1.09 g, 2.6 mmol, 1.0 equiv) and N,N′-dimethyl-ethylene diamine (280 μL, 2.6 mmol, 1.0 equiv). The tube was sealed, evacuated and back-filled with nitrogen, then acetonitrile (5 mL) was added and the reaction mixture was heated at 80° C. overnight. The reaction mixture was cooled, diluted with ethyl acetate and the reaction was quenched with saturated ammonium chloride. The products were extracted with ethyl acetate, the combined organics were washed with brine, dried (MgSO4), filtered and the solvent evaporated. The crude material was purified by column chromatography (SiO2, eluted with petrol—EtOAc 0-100%) to afford 490 mg of [1,3-bis-(4-chloro-phenyl)-2-oxo-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-yl]-(2,4-dimethoxy-benzyl)-carbamic acid tert-butyl ester (high RF compound, MS: [M+H]+=635) and 383 mg of [1-(4-chloro-phenyl)-2-oxo-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-yl]-(2,4-dimethoxy-benzyl)-carbamic acid tert-butyl ester (low RF compound, MS: [M+H]+=525).

1. customInto a reaction tube were placed
2. customThe tube was sealed
3. customevacuated
4. additionback-filled with nitrogen
5. additionacetonitrile (5 mL) was added
6. temperatureThe reaction mixture was cooled
7. additiondiluted with ethyl acetate
8. customthe reaction was quenched with saturated ammonium chloride
9. extractionThe products were extracted with ethyl acetate
10. washthe combined organics were washed with brine
11. dry with materialdried (MgSO4)
12. filtrationfiltered
13. customthe solvent evaporated
14. customThe crude material was purified by column chromatography (SiO2, eluted with petrol—EtOAc 0-100%)