Dimethylmalonic acid → 2,2-Dimethyl-N-pyridin-2-ylmethylmalonamic acid

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 filtrered 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. stirringThe resin was shaken for overnigth
9. filtrationThe resin was filtered
10. washwashed with NMP (5×20 mL) and DCM (10×20 mL)
11. additionTFA/TIS/water (95:2.5:2.5; 30 mL) was added to the resin and it
12. waitwas shaked for 1 hr
13. filtrationfiltered
14. concentrationconcentrated in vacuo

ORD record

ord-8d9733a562a74514989aa817119a1711

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08648041B2