反应详情

A vigorously stirred mixture of 20.1 g (100 mmol) of 1-amino-6-tert-butyl-2,7-naphthyridine S41, 37.4 g (110 mmol) of 2-tert-butyl-3-bromo-4-iodopyridine (S27) or 27.9 g (110 mmol) of 2-trifluoromethyl-4-iodo-5-chloropyridine, 35.0 g (250 mmol) of potassium carbonate, 200 g of glass beads (diameter 3 mm), 2.6 g (10 mmol) of triphenylphosphine and 450 mg (2 mmol) of palladium(II) acetate in 500 ml of o-xylene is heated under reflux until the 1-amino-6-tert-butyl-2,7-naphthyridine has been consumed (typically 3-30 h). After cooling, the solid is filtered off via a silica-gel bed, rinsed with 1000 ml of THF, and the filtrate is evaporated to dryness. The residue is dissolved in 75 ml of ethyl acetate at the boiling temperature, and 250 ml of n-heptane are slowly added. After cooling, the solid which has crystallised out is filtered off with suction, washed twice with 50 ml of n-heptane each time and dried in vacuo. The solids obtained in this way are freed from low-boiling components and non-volatile secondary components by sublimation (p about 1×10−5 mbar, T about 170-200° C.). Purity according to 1H-NMR typically >99.5%.

1. temperatureis heated
2. customhas been consumed (typically 3-30 h)
3. temperatureAfter cooling
4. filtrationthe solid is filtered off via a silica-gel bed
5. washrinsed with 1000 ml of THF
6. customthe filtrate is evaporated to dryness
7. dissolutionThe residue is dissolved in 75 ml of ethyl acetate at the boiling temperature, and 250 ml of n-heptane
8. additionare slowly added
9. temperatureAfter cooling
10. customthe solid which has crystallised out
11. filtrationis filtered off with suction
12. washwashed twice with 50 ml of n-heptane each time
13. customdried in vacuo
14. customThe solids obtained in this way
15. customare freed from low-boiling components and non-volatile secondary components by sublimation (p about 1×10−5 mbar, T about 170-200° C.)