Trichloroacetonitrile → 3,5-diamino-N-[4-(4-methylpiperazin-1-yl)-3-pyridyl]-1H-pyrazole-4-carboxamide

HRID 524845Notes

Reaction equation

HRID 524845 reaction equation
[C:1]([CH2:3][C:4]([NH:6][C:7]1[CH:8]=[N:9][CH:10]=[CH:11][C:12]=1[N:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1)=O)#[N:2].C([O-])(=O)C.[Na+].ClC(Cl)(Cl)[C:27]#[N:28].[OH2:31].[NH2:32][NH2:33]>C(O)C>[NH2:2][C:1]1[C:3]([C:4]([NH:6][C:7]2[CH:8]=[N:9][CH:10]=[CH:11][C:12]=2[N:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[O:31])=[C:27]([NH2:28])[NH:33][N:32]=1

Participants

6

Reactant 4

HCID 11011TrichloroacetonitrileHCID 24654Hydrazine hydrate (1:1)HCID 517045Sodium AcetateHCID 867209002-cyano-N-(4-(4-methylpiperazin-1-yl)pyridin-3-yl)acetamide

Product 1

HCID 867208993,5-diamino-N-[4-(4-methylpiperazin-1-yl)-3-pyridyl]-1H-pyrazole-4-carboxamideYield 51.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a suspension of 2-cyano-N-[4-(4-methylpiperazin-1-yl)-3-pyridyl]acetamide 8 (1.6 g, 6.170 mmol) in ethanol (40 mL) was added sodium acetate (1.052 g, 12.83 mmol), followed by trichloroacetonitrile (1.042 g, 733.8 μL, 7.219 mmol) dropwise. The heterogeneous mixture was stirred at room temperature under an atmosphere of nitrogen for 18h. The reaction mixture was concentrated under vacuum, and the residue was dissolved in NMP (30 mL). Hydrazine hydrate (803 mg, 780.4 mL, 16.04 mmol) was added and the reaction mixture was stirred at room temperature for 3 h. The solvents were removed under vacuum and the residue triturated in DCM to form a brown solid which was isolated by filtration to provide 3,5-diamino-N-[4-(4-methylpiperazin-1-yl)-3-pyridyl]-1H-pyrazole-4-carboxamide 9 (1 g, 51%). MS (ES+) 317.1.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. dissolutionthe residue was dissolved in NMP (30 mL)
  3. stirringthe reaction mixture was stirred at room temperature for 3 h
  4. customThe solvents were removed under vacuum
  5. customthe residue triturated in DCM
  6. customto form a brown solid which
  7. customwas isolated by filtration

Sources & evidence

ORD record
ord-0896618b17fb4f5a90a55c02185dbb72
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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