Sodium hydride → 5-(3-{3,5-difluoro-4-[3-(4-methylpiperazin-1-yl)propoxy]-phenyl}-6-oxo-6H-pyridazin-1-ylmethyl)-1,3-dihydrobenzimidazol-2-one

HRID 2093353Notes

Reaction equation

HRID 2093353 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[H-].[Na+].[O:14]=[C:15]1[N:20]([CH2:21][C:22]2[CH:31]=[CH:30][C:25]3[NH:26][C:27](=[O:29])[NH:28][C:24]=3[CH:23]=2)[N:19]=[C:18]([C:32]2[CH:37]=[C:36]([F:38])[C:35](F)=[C:34]([F:40])[CH:33]=2)[CH:17]=[CH:16]1>CN(C=O)C>[F:38][C:36]1[CH:37]=[C:32]([C:18]2[CH:17]=[CH:16][C:15](=[O:14])[N:20]([CH2:21][C:22]3[CH:31]=[CH:30][C:25]4[NH:26][C:27](=[O:29])[NH:28][C:24]=4[CH:23]=3)[N:19]=2)[CH:33]=[C:34]([F:40])[C:35]=1[O:11][CH2:10][CH2:9][CH2:8][N:5]1[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 792083-(4-Methyl-1-piperazine)propan-1-olHCID 594068205-[6-Oxo-3-(3,4,5-trifluorophenyl)-6H-pyridazin-1-ylmethyl]-1,3-dihydrobenzimidazol-2-one

Product 1

HCID 250988755-(3-{3,5-difluoro-4-[3-(4-methylpiperazin-1-yl)propoxy]-phenyl}-6-oxo-6H-pyridazin-1-ylmethyl)-1,3-dihydrobenzimidazol-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

170 mg (1.08 mmol) of 3-(4-methylpiperazin-1-yl)propan-1-ol are dissolved in 20 ml of DMF, 64.5 mg (1.61 mmol) of NaH in paraffin oil (60%) are added under nitrogen, and the mixture is stirred at room temperature. After 10 min, 200 mg (0.54 mmol) of 5-[6-oxo-3-(3,4,5-tri-fluorophenyl)-6H-pyridazin-1-ylmethyl]-1,3-dihydrobenzimidazol-2-one are added, and the mixture is stirred at room temperature under a nitrogen atmosphere. The reaction is monitored by means of HPLC. After 3 h, the reaction is terminated. The mixture is neutralised using 1N HCl. The mixture is evaporated to dryness, the residue is dissolved in 100 ml of ethyl acetate and 30 ml of water, the aqueous phase is separated off and neutralised using sodium hydrogencarbonate and subsequently extracted. A precipitate deposits in the process and is separated off. The residue is stirred with methanol, filtered off with suction and dried in vacuo.

Workup

  1. stirringthe mixture is stirred at room temperature under a nitrogen atmosphere
  2. waitAfter 3 h
  3. customthe reaction is terminated
  4. customThe mixture is evaporated to dryness
  5. dissolutionthe residue is dissolved in 100 ml of ethyl acetate
  6. custom30 ml of water, the aqueous phase is separated off
  7. extractionsubsequently extracted
  8. customA precipitate deposits in the process and is separated off
  9. stirringThe residue is stirred with methanol
  10. filtrationfiltered off with suction
  11. customdried in vacuo

Sources & evidence

ORD record
ord-3d84dadb4a1e4a2ab674b39979dae7f2
Source dataset
uspto-grants-2013_05
Patent number
US08445489B2

Reaction notes

Loading…