1,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)- → (S)-tert-Butyl 2-(2-carbamoyl-1H-pyrrol-1-ylcarbamoyl)pyrrolidine-1-carboxylate

HRID 218307Notes

Reaction equation

HRID 218307 reaction equation
[NH2:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]([NH2:9])=[O:8].[C:10]([O:14][C:15]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[C:22](O)=[O:23])=[O:16])([CH3:13])([CH3:12])[CH3:11].Cl.CN(C)CCCN=C=NCC>C1COCC1>[C:7]([C:3]1[N:2]([NH:1][C:22]([C@@H:18]2[CH2:19][CH2:20][CH2:21][N:17]2[C:15]([O:14][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:16])=[O:23])[CH:6]=[CH:5][CH:4]=1)(=[O:8])[NH2:9]

Participants

5

Reactant 3

HCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 104191801-Amino-1H-pyrrole-2-carboxamide

Product 1

HCID 59313671(S)-tert-Butyl 2-(2-carbamoyl-1H-pyrrol-1-ylcarbamoyl)pyrrolidine-1-carboxylateYield 86.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-amino-1H-pyrrole-2-carboxamide (3.00 g, 24.0 mmol) and (S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (7.18 g, 28.8 mmol) was dissolved in THF (240 mL). To this solution was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (5.52 g, 28.8 mmol). The reaction was stirred overnight at rt, then concentrated in vacuo. The crude residue was dissolved in CH2Cl2 then washed with water (3×200 mL) and brine (200 mL). The organic layer was dried (MgSO4), filtered, and concentrated in vacuo to a sticky gum, which was dissolved in a 1:1 solution of CH2Cl2/Hex, then concentrated in vacuo to remove most of the CH2Cl2. The precipitate that formed was filtered and dried to give 1A (6.68 g, 78%). 1A had an analytical HPLC retention time=2.132 min (Phenomenex Luna 3.0×50 mm, 10-90% aqueous MeOH over 5 min containing 0.1% TFA) and a LC/MS M++1=357.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe crude residue was dissolved in CH2Cl2
  3. washthen washed with water (3×200 mL) and brine (200 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to a sticky gum, which
  7. dissolutionwas dissolved in a 1:1 solution of CH2Cl2/Hex
  8. concentrationconcentrated in vacuo
  9. customto remove most of the CH2Cl2
  10. customThe precipitate that formed
  11. filtrationwas filtered
  12. customdried

Sources & evidence

ORD record
ord-2b0be125a2c04667abf34986b159bf78
Source dataset
uspto-grants-2012_06
Patent number
US08198438B2

Reaction notes

Loading…