反应详情

温度

20 °C

To a suspension of 2-(formyl-3-methoxyphenoxy)ethyl polystyrene (AMEBA) resin (ex Novabiochem) (2.13 g, 3.40 mmol) in a mixture of acetic acid/DMF (60 ml, 1:100 v/v) is added 2-amino-3-tert-butoxy-propan-1-ol and sodium triacetoxyborohydride (1.44 g, 6.80 mmol) and the mixture is shaken for 18 hours at 20° C., then filtered. The resin obtained is washed with methanol, DMF and dichloromethane (DCM), then dried under vacuum. A THF/acetonitrile mixture (20 ml, 1:1 v/v) is added to the dried resin followed by iodine (4.30 g, 18.85 mmol), imidazole (1.16 g, 17.00 mmol) and triphenylphosphine (4.46 g, 17.00 mmol). The suspension obtained is shaken for 6 hours at 20° C., then filtered. The resin is washed with THF and dried under vacuum. To the freshly prepared resin obtained (0.30 g, 0.48 mmol) is added a solution of 4-(4-fluoro-phenoxy)-piperidine (309 mg, 1.00 mmol) dissolved in DMF (2 ml) and diisopropylethylamine (62.4 mg, 0.48 mmol). The mixture is heated at 55° C. for 8 hours. The resulting mixture is filtered and the resin is washed with DMF. To the washed resin are added (E)-3-(5-cyano-2-methoxy-phenyl)-acrylic acid (0.27 g, 1.05 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluoro-phosphate (547 mg, 1.44 mmol) diisopropylethylamine (186 mg, 1.44 mmol) and DMF (4 ml) and the mixture is shaken at 20° C. for 18 hours, then washed with DMF and methanol, after which it is treated with trifluoroacetic acid/DCM (6 ml, 1:1 v/v) at 20° C. for 1 hour to remove the product from the resin. The resulting mixture is filtered and the filtrate evaporated under vacuum to give the product, [MH]+ 453.9.

1. filtrationfiltered
2. customThe resin obtained
3. washis washed with methanol, DMF and dichloromethane (DCM)
4. customdried under vacuum
5. additionA THF/acetonitrile mixture (20 ml, 1:1 v/v) is added to the dried resin
6. customThe suspension obtained
7. stirringis shaken for 6 hours at 20° C.
8. filtrationfiltered
9. washThe resin is washed with THF
10. customdried under vacuum
11. customTo the freshly prepared resin obtained (0.30 g, 0.48 mmol)
12. temperatureThe mixture is heated at 55° C. for 8 hours
13. filtrationThe resulting mixture is filtered
14. washthe resin is washed with DMF
15. stirringthe mixture is shaken at 20° C. for 18 hours
16. washwashed with DMF and methanol
17. additionafter which it is treated with trifluoroacetic acid/DCM (6 ml, 1:1 v/v) at 20° C. for 1 hour
18. customto remove the product from the resin
19. filtrationThe resulting mixture is filtered
20. customthe filtrate evaporated under vacuum
21. customto give the product, [MH]+ 453.9