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 filtrered 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. stirringThe resin was shaken for 2 days
9. filtrationThe resin was filtered
10. washwashed with NMP (5×20 mL) and DCM (10×20 mL)
11. addition2,2,2-Trifluoroethanol/dichlormethan 1:1 (20 mL) was added to the resin and it
12. waitwas shaked for 2 hrs
13. washThe resin was washed with 2,2,2-Trifluoroethanol/dichlormethan 1:1 (10 mL)
14. customthe combined filtrates were collected
15. concentrationconcentrated in vacuo