Sodium hydride → (6-Chloro-imidazo[1,2-b]pyridazin-8-yl)-[5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-yl]-amine

HRID 402933Notes

Reaction equation

HRID 402933 reaction equation
Br[C:2]1[C:3]2[N:4]([CH:9]=[CH:10][N:11]=2)[N:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:12][N:13]1[CH2:18][CH2:17][N:16]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([NH2:26])=[N:24][CH:25]=2)[CH2:15][CH2:14]1.[H-].[Na+]>CN(C=O)C>[Cl:8][C:6]1[CH:7]=[C:2]([NH:26][C:23]2[CH:22]=[CH:21][C:20]([CH2:19][N:16]3[CH2:15][CH2:14][N:13]([CH3:12])[CH2:18][CH2:17]3)=[CH:25][N:24]=2)[C:3]2[N:4]([CH:9]=[CH:10][N:11]=2)[N:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 468352698-Bromo-6-chloroimidazo(1,2-b)pyridazineHCID 592929015-((4-Methylpiperazin-1-yl)methyl)pyridin-2-amine

Product 1

HCID 86686832(6-Chloro-imidazo[1,2-b]pyridazin-8-yl)-[5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-yl]-amineYield 51.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 8-bromo-6-chloroimidazo[1,2-b]pyridazine (214 mg, 921 μmol, Eq: 0.95) and 5-((4-methylpiperazin-1-yl)methyl)pyridin-2-amine (200 mg, 970 μmol, Eq: 1.00) in DMF (10.0 ml) was cooled to 0° C. To this was added sodium hydride (60% in mineral oil, 124 mg, 3.1 mmol, Eq: 3.2). The reaction was allowed to stir at 0° C. for 10 min and then allowed to warm to room temperature and stirred for 72 h. The reaction was quenched with saturated NaHCO3 (aq) and then diluted with water and EtOAc. The organic layer was separated and the aqueous phase was washed with EtOAc. The organic layers were combined, dried over MgSO4 and concentrated in vacuo. The residue was dissolved in Et2O. The organic layer was washed with water and dried over MgSO4. The drying agent was removed by filtration. The resulting solution was concentrated in vacuo to give (6-chloro-imidazo[1,2-b]pyridazin-8-yl)-[5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-yl]-amine (170 mg, 49%) as a solid. LC/MS-ESI observed [M+H]+ 358.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 72 h
  3. customThe reaction was quenched with saturated NaHCO3 (aq)
  4. additiondiluted with water and EtOAc
  5. customThe organic layer was separated
  6. washthe aqueous phase was washed with EtOAc
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in Et2O
  10. washThe organic layer was washed with water
  11. dry with materialdried over MgSO4
  12. customThe drying agent was removed by filtration
  13. concentrationThe resulting solution was concentrated in vacuo

Sources & evidence

ORD record
ord-6820a6d164884e0bad4a2fb02a5c206a
Source dataset
uspto-grants-2014_06
Patent number
US08742098B2

Reaction notes

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