1,2-Dichloroethane → (2S,4S)-1-Boc-4-azido-2-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidine

HRID 2063961Notes

Reaction equation

HRID 2063961 reaction equation
[C:1]([N:8]1[CH2:12][C@@H:11]([N:13]=[N+:14]=[N-:15])[CH2:10][C@H:9]1[C:16]([OH:18])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CCN(C(C)C)C(C)C.[CH3:28][N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[C:1]([N:8]1[CH2:12][C@@H:11]([N:13]=[N+:14]=[N-:15])[CH2:10][C@H:9]1[C:16]([N:32]1[CH2:33][CH2:34][N:29]([CH3:28])[CH2:30][CH2:31]1)=[O:18])([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 12094910(2S,4S)-4-azido-1-[(tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 86641588(2S,4S)-1-Boc-4-azido-2-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidineYield 98.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2S,4S)-1-Boc-4-azidopyrrolidine-2-carboxylic acid (9.5 g, 35 mmol) obtained in Step A was dissolved in DMF (30 mL). After DIPEA (1.15 mL, 6.70 mmol) was added thereto, 1-methylpiperazine (5.81 mL, 52.5 mmol), HOBT (7 g, 52.5 mmol) and EDC (10.2 g, 52.5 mmol) were added thereto, in turn. The reaction solution was stirred for 12 hours at room temperature and concentrated in vacuo. The residue was diluted with EtOAc and washed with saturated NaHCO3 aqueous solution, water and 1N HCl. The extracted organic solution was dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (eluent: MC/MeOH=10/1) to give the title compound (11.67 g, 93%).

Workup

  1. concentrationconcentrated in vacuo
  2. additionThe residue was diluted with EtOAc
  3. washwashed with saturated NaHCO3 aqueous solution, water and 1N HCl
  4. dry with materialThe extracted organic solution was dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (eluent: MC/MeOH=10/1)

Sources & evidence

ORD record
ord-4b3e77136be141d9bbec8ddb528df9a4
Source dataset
uspto-grants-2012_10
Patent number
US08288386B2

Reaction notes

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