1-benzyl hydrogen (R)-pyrrolidine-1,2-dicarboxylate → (R)-Benzyl 2-(2-carbamoyl-1H-pyrrol-1-ylcarbamoyl)pyrrolidine-1-carboxylate

HRID 218309Notes

Reaction equation

HRID 218309 reaction equation
[NH2:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]([NH2:9])=[O:8].[CH2:10]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH2:22][C@@H:21]1[C:25](O)=[O:26])=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.Cl.CN(C)CCCN=C=NCC>C1COCC1>[C:7]([C:3]1[N:2]([NH:1][C:25]([C@H:21]2[CH2:22][CH2:23][CH2:24][N:20]2[C:18]([O:17][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:19])=[O:26])[CH:6]=[CH:5][CH:4]=1)(=[O:8])[NH2:9]

Participants

5

Reactant 3

HCID 1112081-benzyl hydrogen (R)-pyrrolidine-1,2-dicarboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 104191801-Amino-1H-pyrrole-2-carboxamide

Product 1

HCID 59313679(R)-Benzyl 2-(2-carbamoyl-1H-pyrrol-1-ylcarbamoyl)pyrrolidine-1-carboxylateYield 103.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-amino-1H-pyrrole-2-carboxamide (6.00 g, 48.0 mmol) and (R)-1-(benzyloxycarbonyl)pyrrolidine-2-carboxylic acid (14.3 g, 57.5 mmol) was dissolved in THF (480 mL). To this solution was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (11.0 g, 57.5 mmol). The reaction was stirred overnight at rt then concentrated in vacuo. The residue was dissolved in CH2Cl2 (400 mL), washed with water (3×400 mL) and brine (400 mL), then dried (MgSO4), filtered, and concentrated in vacuo to give slightly impure 11A (17.65 g, >100%). 11A had an analytical HPLC retention time=2.103 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. concentrationthen concentrated in vacuo
  2. dissolutionThe residue was dissolved in CH2Cl2 (400 mL)
  3. washwashed with water (3×400 mL) and brine (400 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-adb671ecf4ba4c06acd66714f80f01a6
Source dataset
uspto-grants-2012_06
Patent number
US08198438B2

Reaction notes

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