1-Methylpiperazine → (2S,4S)-1-BOC-4-[acetyl(4,4-dimethylcyclohexyl)amino]-2-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidine

HRID 1927555Notes

Reaction equation

HRID 1927555 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](O)=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CCN(C(C)C)C(C)C.[CH3:37][N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]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[CH2:22][CH2:21][C:20]([CH3:23])([CH3:24])[CH2:19][CH2:18]2)[CH2:13][C@H:9]1[C:10]([N:41]1[CH2:42][CH2:43][N:38]([CH3:37])[CH2:39][CH2:40]1)=[O:11])([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

6

Reactant 4

HCID 531671-MethylpiperazineHCID 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 67359166(2S,4S)-1-BOC-4-[acetyl(4,4-dimethylcyclohexyl)amino]-2-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidineYield 95%

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 was dissolved in DMF (10 mL) and DIPEA (1.05 mL, 6.01 mmol) was added thereto. 1-methylpiperazine (0.32 mL, 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 and purified by column chromatography (eluent: MC/MeOH=10/1) to give the title compound (1.06 g, 95%).

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. custompurified by column chromatography (eluent: MC/MeOH=10/1)

Sources & evidence

ORD record
ord-184376e1d8084f7aaedff8777eaabfe1
Source dataset
uspto-grants-2012_05
Patent number
US08183243B2

Reaction notes

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