Methanesulfonic Acid → N1-(cyanomethyl)-N2-[1-methyl-4-(4-piperazin-1-ylphenyl)-1H-pyrazol-3-yl]leucinamide

HRID 1744118Notes

Reaction equation

HRID 1744118 reaction equation
[C:1]([CH2:3][NH:4][C:5](=[O:37])[C@H:6]([CH2:33][CH:34]([CH3:36])[CH3:35])[NH:7][C:8]1[C:12]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]3)=[CH:15][CH:14]=2)=[CH:11][N:10]([CH3:32])[N:9]=1)#[N:2].CS(O)(=O)=O.C([O-])(O)=O.[Na+]>C1COCC1>[C:1]([CH2:3][NH:4][C:5](=[O:37])[C@H:6]([CH2:33][CH:34]([CH3:35])[CH3:36])[NH:7][C:8]1[C:12]([C:13]2[CH:14]=[CH:15][C:16]([N:19]3[CH2:20][CH2:21][NH:22][CH2:23][CH2:24]3)=[CH:17][CH:18]=2)=[CH:11][N:10]([CH3:32])[N:9]=1)#[N:2]

Participants

5

Reactant 3

HCID 6395Methanesulfonic AcidHCID 516892Sodium BicarbonateHCID 86594569N1-(cyanomethyl)-N2-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-1-methyl-1H-pyrazol-3-yl)leucinamide

Product 1

HCID 86594570N1-(cyanomethyl)-N2-[1-methyl-4-(4-piperazin-1-ylphenyl)-1H-pyrazol-3-yl]leucinamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To N1-(cyanomethyl)-N2-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-1-methyl-1H-pyrazol-3-yl)leucinamide (144 mg, 0.283 mmol) in dry THF (0.5 mL) under dry nitrogen was gradually added a total of 5 equivalents of MeSO3H (100 μL, 1.42 mmol) over a period of 4 hours in portions of 1–2 equivalents at a time and the reaction mixture was stirred overnight. Aqueous sat. NaHCO3 was added carefully and the product was extracted with EtOAc (2×), dried over Na2SO4, concentrated in vacuo, and purified by flash chromatography over silica gel (NH4OH/MeOH/CH2Cl2, 1/9/90) to afford N1-(cyanomethyl)-N2-[1-methyl-4-(4-piperazin-1-ylphenyl)-1H-pyrazol-3-yl]leucinamide. MS (−ESI): 408.4 [M−1]−.

Workup

  1. extractionthe product was extracted with EtOAc (2×)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. custompurified by flash chromatography over silica gel (NH4OH/MeOH/CH2Cl2, 1/9/90)

Sources & evidence

ORD record
ord-f3997197e3064adba48be4b3a7d79a03
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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