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

HRID 2408308Notes

Reaction equation

HRID 2408308 reaction equation
ClC1C=CC=CC=1C(Cl)(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:22][C:23]([CH3:30])([C:27](O)=[O:28])[C:24]([OH:26])=[O:25].CCN(C(C)C)C(C)C.C1C=NC2N(O)N=NC=2C=1.CC(C)N=C=NC(C)C.[NH2:59][CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][N:62]=1>C(Cl)Cl.CN1C(=O)CCC1.C(Cl)Cl.CN1C(=O)CCC1>[CH3:22][C:23]([CH3:30])([C:27]([NH:59][CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][N:62]=1)=[O:28])[C:24]([OH:26])=[O:25]

Participants

10

Reactant 6

HCID 11686Dimethylmalonic acidHCID 12734DiisopropylcarbodiimideHCID 195092-PyridinemethanamineHCID 81531Diisopropylethylamine2×HCID 945242-Chlorotrityl chlorideHCID 181649HOAt

Product 1

HCID 583390472,2-Dimethyl-N-pyridin-2-ylmethylmalonamic acid

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent2×HCID 19383075dichloromethane N-methyl-2-pyrrolidoneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-7e47a7f974a942db9ff6ec844c45c1bb
Source dataset
uspto-grants-2014_08
Patent number
US08815802B2

Reaction notes

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