Piperazine → (2S,4S)-1-BOC-4-[acetyl(4,4-dimethylcyclohexyl)amino]-2-(piperazin-1-ylcarbonyl)pyrrolidine

HRID 1666019Notes

Reaction equation

HRID 1666019 reaction equation
[C:1]([N:8]1[CH2:15][C@@H:14]([N:16]([C:25](=[O:27])[CH3:26])[CH:17]2[CH2:22][CH2:21][C:20]([CH3:24])([CH3:23])[CH2:19][CH2:18]2)[CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CCN(C(C)C)C(C)C.[NH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:1]([N:8]1[CH2:15][C@@H:14]([N:16]([C:25](=[O:27])[CH3:26])[CH:17]2[CH2:18][CH2:19][C:20]([CH3:24])([CH3:23])[CH2:21][CH2:22]2)[CH2:13][C@H:9]1[C:10]([N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)=[O:12])([O:3][C:4]([CH3:7])([CH3:5])[CH3:6])=[O:2]

Participants

6

Reactant 4

HCID 4837PiperazineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67357391(4S)-1-BOC-4-[acetyl(4,4-dimethylcyclohexyl)amino]-L-proline

Product 1

HCID 67357600(2S,4S)-1-BOC-4-[acetyl(4,4-dimethylcyclohexyl)amino]-2-(piperazin-1-ylcarbonyl)pyrrolidineYield 93%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(4S)-1-BOC-4-[acetyl(4,4-dimethylcyclohexyl)amino]-L-proline (0.92 g, 2.41 mmol) obtained in Step C of Example 1, was dissolved in DMF (10 mL) and DIPEA (1.05 mL, 6.01 mmol) was added thereto. Piperazine (0.25 g, 2.89 mmol) and HBTU (0.91 g, 2.41 mmol) were also added thereto in order. After the reaction solution was stirred at room temperature for 2 hours, the solution was concentrated in vacuo. The residue was diluted with EtOAc and washed with saturated NaHCO3 aqueous solution. The extracted organic solution was dried over MgSO4, concentrated in vacuo. The residue was purified by column chromatography (eluent: MC/MeOH=10/1) to give the title compound (1.01 g, 93%).

Workup

  1. concentrationthe solution was concentrated in vacuo
  2. additionThe residue was diluted with EtOAc
  3. washwashed with saturated NaHCO3 aqueous solution
  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-341074ad34a04c8388f2dac68b5a0ce2
Source dataset
uspto-grants-2011_10
Patent number
US08039622B2

Reaction notes

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