Methanesulfonic Acid → N-(cyanomethyl)-4-methyl-2-{[4'-(1-piperazinyl)[1,1'-biphenyl]-2-yl]methyl}pentanamide

HRID 1744074Notes

Reaction equation

HRID 1744074 reaction equation
[C:1]([CH2:3][NH:4][C:5]([CH:7]([CH2:34][CH:35]([CH3:37])[CH3:36])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]2)=[CH:17][CH:16]=1)=[O:6])#[N:2].CS(O)(=O)=O.C([O-])(O)=O.[Na+]>C1COCC1>[C:1]([CH2:3][NH:4][C:5](=[O:6])[CH:7]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]1[CH:16]=[CH:17][C:18]([N:21]2[CH2:22][CH2:23][NH:24][CH2:25][CH2:26]2)=[CH:19][CH:20]=1)[CH2:34][CH:35]([CH3:36])[CH3:37])#[N:2]

Participants

5

Reactant 3

HCID 6395Methanesulfonic AcidHCID 516892Sodium BicarbonateHCID 22235962Tert-butyl 4-[2'-(2-{[(cyanomethyl)amino]carbonyl}-4-methylpentyl)[1,1'-biphenyl]-4-yl]-1-piperazinecarboxylate

Product 1

HCID 10158123N-(cyanomethyl)-4-methyl-2-{[4'-(1-piperazinyl)[1,1'-biphenyl]-2-yl]methyl}pentanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To tert-butyl 4-[2′-(2-{[(cyanomethyl)amino]carbonyl}-4-methylpentyl)[1,1′-biphenyl]-4-yl]-1-piperazinecarboxylate (407 mg, 0.808 mmol) in dry THF (10 mL) under dry nitrogen was gradually added a total of 6.5 equivalents of MeSO3H (total of 340 μL, 5.25 mmol) over a period of 3 days in portions of 1–2 equivalents at a time. Aqueous sat. NaHCO3 was added carefully and the product extracted with EtOAc (3×), dried over Na2SO4, concentrated in vacuo, and purified by flash chromatography over silica gel (NH4/OH/MeOH/CH2Cl2, 1/9/90) to afford N-(cyanomethyl)-4-methyl-2-{[4′-(1-piperazinyl)[1,1′-biphenyl]-2-yl]methyl}pentanamide.

Workup

  1. extractionthe product extracted with EtOAc (3×)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. custompurified by flash chromatography over silica gel (NH4/OH/MeOH/CH2Cl2, 1/9/90)

Sources & evidence

ORD record
ord-28ee07fe6cd146d68d16a7c266dbddfe
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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