反应详情

To a suspension of N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(4-morpholinylmethyl)-3-quinolinecarboxamide (581.4 mg) and PdCl2(PPh3)2 (37.9 mg) in Et3N (20 mL) is added CuI (10.3 mg) and 3-butyn-1-ol (0.082 mL). The reaction is stirred at room temperature for 2 days under N2. After 2 days the solvent evaporates. The resulting solid is dissolved in CH2Cl2 and partitioned against H2O. The aqueous layer is extracted with CH2Cl2 (2×). The combined organic layers are washed with brine (1×), dried over Na2SO4, filtered, and condensed. The crude solid is adsorbed onto silica and chromatographed (Biotage flash 40S, gradient from CH2Cl2 to 3% MeOH in CH2Cl2). Product-containing fractions are combined and concentrated to yield a creme solid. The solid is recrystallized from hot acetonitrile to afford 290 mg (56%) of N-(4-chlorobenzyl)-2-(2-hydroxyethyl)-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide as an off-white solid, m.p. 169-172° C.

1. customAfter 2 days the solvent evaporates
2. dissolutionThe resulting solid is dissolved in CH2Cl2
3. custompartitioned against H2O
4. extractionThe aqueous layer is extracted with CH2Cl2 (2×)
5. washThe combined organic layers are washed with brine (1×)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. customcondensed
9. customchromatographed (Biotage flash 40S, gradient from CH2Cl2 to 3% MeOH in CH2Cl2)
10. concentrationconcentrated
11. customto yield a creme solid
12. customThe solid is recrystallized from hot acetonitrile