反应详情

2-Chlorotrityl chloride resin (2.3 g, 3.0 mmol) was swelled in DCM for 20 mins and filtered. Dimethylmalonic acid (2 eq; 6.0 mmol; 793 mg) was dissolved i DCM:DMF 1:1 (10 mL) and added to the resin followed by DIPEA (6 eq; 18.0 mmol; 3.14 mL) and DCM (10 mL). The resin was shaken overnight at RT. The resin was filtered and washed with DCM:MeOH:DIPEA (17:2:1), DCM, NMP og DCM (2×25 mL of each). The resin was swelled in DMF for 20 mins and filtered. HOAt (3 eq; 9.0 mmol; 1.23 g), DIC (3 eq; 9.0 mmol; 1.40 mL) and DMF (25 mL) was added and the resin was shaken for 90 min at RT. The resin was filtered and 3-(1-Trityl-1H-imidazol-4-yl)-propyl amine (1.8 eq; 5.40 mmol; 1.84 g), DIPEA (4 eq; 6.0 mmol; 2.09 mL), and DMF (10 mL) was added. The resin was shaken for 2 days. The resin was filtered and washed with NMP (5×20 mL) and DCM (10×20 mL). 2,2,2-Trifluoroethanol/dichlormethan 1:1 (20 mL) was added to the resin and it was shaked for 2 hrs. The resin was washed with 2,2,2-Trifluoroethanol/dichlormethan 1:1 (10 mL) and the combined filtrates were collected and concentrated in vacuo to yield the title compound.

1. filtrationfiltered
2. additionadded to the resin
3. filtrationThe resin was filtered
4. washwashed with DCM:MeOH:DIPEA (17:2:1), DCM, NMP og DCM (2×25 mL of each)
5. waitThe resin was swelled in DMF for 20 mins
6. filtrationfiltered
7. stirringthe resin was shaken for 90 min at RT
8. filtrationThe resin was filtered
9. stirringThe resin was shaken for 2 days
10. filtrationThe resin was filtered
11. washwashed with NMP (5×20 mL) and DCM (10×20 mL)
12. addition2,2,2-Trifluoroethanol/dichlormethan 1:1 (20 mL) was added to the resin and it
13. waitwas shaked for 2 hrs
14. washThe resin was washed with 2,2,2-Trifluoroethanol/dichlormethan 1:1 (10 mL)
15. customthe combined filtrates were collected
16. concentrationconcentrated in vacuo