反应详情

Catechol borane (2.7 mL, 1M tetrahydrofuran solution, 2.7 mmol) was added dropwise to ethoxyacetylene (0.7 mL, 40% hexane solution, 2.83 mmol) on an ice bath, and the mixture was stirred for 1 hour at room temperature. The mixture was further heated at 70° C. and stirred for 2 hours, and allowed to room temperature. A solution of 2,6-diamino-5-iodo-nicotinic acid ethyl ester described in Preparation Example R-1 (415 mg, 1.35 mmol) in tetrahydrofuran (5.5 mL), tetrakis(triphenylphosphine)palladium(0) (48 mg, 0.042 mmol) and sodium hydroxide (160 mg, 4 mmol, powder) were added thereto, followed by stirring for 7 hours 30 minutes under reflux. The reaction mixture was allowed to room temperature, 2N hydrochloric acid (4.7 mL, 9.4 mmol) was added thereto, followed by stirring for 60 hours at room temperature. After the reaction was completed, the reaction mixture was evaporated, and extracted using diethyl ether. The aqueous layer was fractionated, neutralized on an ice bath with an aqueous solution of 5N sodium hydroxide, then, was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, then evaporated, the resulting residue was purified by silica gel column chromatography (ethyl acetate:hexane=2:1), and the title compound (97 mg, 0.47 mmol, 35%) was obtained.

1. temperatureThe mixture was further heated at 70° C.
2. stirringstirred for 2 hours
3. customallowed to room temperature
4. stirringby stirring for 7 hours 30 minutes
5. temperatureunder reflux
6. customwas allowed to room temperature
7. stirringby stirring for 60 hours at room temperature
8. customthe reaction mixture was evaporated
9. extractionextracted
10. customneutralized on an ice bath with an aqueous solution of 5N sodium hydroxide
11. extractionwas extracted with ethyl acetate
12. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
13. customevaporated
14. customthe resulting residue was purified by silica gel column chromatography (ethyl acetate:hexane=2:1)