反应详情

温度

50 °C

To a 1-L round-bottom, 3-necked flask equipped with magnetic stirring, dynamic nitrogen inlet, and thermocouple probe were added 1-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]ethanone hydrochloride (53.3 g, 0.302 mol), DCE (250 mL), and Et3N (100 mL, 1.006 mol). The flask was warmed to 50° C. and aged for 20 min. An additional 100 mL of DCE was added to facilitate stirring. The solution was cooled to 40° C. and the solution was then added via cannula to a 2-L round-bottom, 3-necked flask equipped with overhead mechanical stirring, dynamic nitrogen inlet, and thermocouple probe containing 4-(thiazolo[4,5-b]pyridin-2-yloxy)-benzaldehyde (51.6 grams, 0.201 mol) dissolved in DCE (100 mL). The 1-L round-bottom flask was rinsed with DCE (100 mL). The rinse solvent was added to the reaction mixture. The resultant deep purple solution was aged at rt for 2.5 h. After such time, the sodium triacetoxyborohydride (72.5 g, 0.342) was added in 4 equal portions over a four-hour period. Once addition was complete, the resultant solution was aged at rt overnight. The reaction was quenched by the slow addition of water (1 L) over a 10-minute period. After 30 additional minutes of stirring, the solution was filtered to remove a fine rag layer of precipitate. The layers were separated and the aqueous layer was extracted with DCE (1×500 mL). The organic layers were combined, washed with brine, dried over MgSO4, filtered and concentrated to yield crude product as a thick brown oil. The crude product was suspended in EtOAc (500 mL), warmed to 70° C., and cooled slowly to rt. The resultant slurry was filtered and the filtrate was concentrated to yield 1-{5-[4-(thiazolo[4,5-b]pyridin-2-yloxy)-benzyl]-2,5-diaza-bicyclo[2.2.1]hept-2-yl}-ethanone (67.2 g, 0.177 mol) as a brown glass. MS (ESI): mass calcd. for C20H20N4O2S, 380.13; m/z found, 381.1 [M+H]+.

1. customTo a 1-L round-bottom, 3-necked flask equipped with magnetic stirring, dynamic nitrogen inlet
2. temperatureThe solution was cooled to 40° C.
3. additionthe solution was then added via cannula to a 2-L round-bottom, 3-necked flask
4. customequipped with overhead mechanical stirring, dynamic nitrogen inlet
5. washThe 1-L round-bottom flask was rinsed with DCE (100 mL)
6. additionThe rinse solvent was added to the reaction mixture
7. additionAfter such time, the sodium triacetoxyborohydride (72.5 g, 0.342) was added in 4 equal portions over a four-hour period
8. additionOnce addition
9. waitthe resultant solution was aged at rt overnight
10. customThe reaction was quenched by the slow addition of water (1 L) over a 10-minute period
11. stirringAfter 30 additional minutes of stirring
12. filtrationthe solution was filtered
13. customto remove a fine rag layer of precipitate
14. customThe layers were separated
15. extractionthe aqueous layer was extracted with DCE (1×500 mL)
16. washwashed with brine
17. dry with materialdried over MgSO4
18. filtrationfiltered
19. concentrationconcentrated
20. customto yield crude product as a thick brown oil
21. temperaturewarmed to 70° C.
22. temperaturecooled slowly to rt
23. filtrationThe resultant slurry was filtered
24. concentrationthe filtrate was concentrated