反应详情

A flame-dried flask under an atmosphere of nitrogen gas containing N-(4-chlorobenzyl)-8-iodo-1-methyl-6-(morpholin-4-ylmethyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (Preparation # 15) (0.55 g) is treated with copper (I) iodide (0.02 g) and dichlorobis(triphenylphosphine)palladium (II) (0.07 g). The solids are treated with dimethylformamide (DMF) (6 mL) and diethylamine (6 mL). The resulting suspension is treated with 4-pentyn-2-ol (0.2 mL) and stirred for 4 days. The reaction is concentrated under reduced pressure and the residue is partitioned between ethyl acetate and phosphate buffer (pH=7). The aqueous phase is extracted with dichloromethane:ethyl acetate. The combined organic layers are washed with phosphate buffer (pH=7), brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue is flash column chromatographed on silica eluting with 5% to 11% methanol in ethyl acetate. The product-containing fractions are combined and concentrated under reduced pressure. The resulting material is crystallized from acetonitrile:methanol and then re-crystallized from toluene to afford the title compound (0.33 g) as off-white solid.

1. concentrationThe reaction is concentrated under reduced pressure
2. customthe residue is partitioned between ethyl acetate and phosphate buffer (pH=7)
3. extractionThe aqueous phase is extracted with dichloromethane
4. washThe combined organic layers are washed with phosphate buffer (pH=7), brine
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customchromatographed on silica eluting with 5% to 11% methanol in ethyl acetate
9. concentrationconcentrated under reduced pressure
10. customThe resulting material is crystallized from acetonitrile
11. custommethanol and then re-crystallized from toluene