反应详情

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:NMP 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 NMP for 20 mins and filtered. HOAt (3 eq; 9.0 mmol; 1.23 g), DIC (3 eq; 9.0 mmol; 1.40 mL) and NMP (25 mL) was added and the resin was shaken for 90 min at RT. The resin was filtered and 2-(Aminomethyl)pyridine (2 eq; 6 mmol; 659 mg), DIPEA (4 eq; 6.0 mmol; 2.09 mL), and NMP (10 mL) was added. The resin was shaken for overnigth. The resin was filtered and washed with NMP (5×20 mL) and DCM (10×20 mL). TFA/TIS/water (95:2.5:2.5; 30 mL) was added to the resin and it was shaked for 1 hr, filtered 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 NMP 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 overnigth
10. filtrationThe resin was filtered
11. washwashed with NMP (5×20 mL) and DCM (10×20 mL)
12. additionTFA/TIS/water (95:2.5:2.5; 30 mL) was added to the resin and it
13. waitwas shaked for 1 hr
14. filtrationfiltered
15. concentrationconcentrated in vacuo