Water → [2-(1H-benzimidazol-2-ylsulfanylmethyl)-3-chloropyridin-4-yl]-methyl-[2-(3-nitroimidazo[1,2-b]pyridazin-6-yloxy)-ethyl]amine hydrochloride

HRID 1637646Notes

Reaction equation

HRID 1637646 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10][CH2:11][C:12]1[C:17]([Cl:18])=[C:16]([N:19]([CH3:23])[CH2:20][CH2:21][OH:22])[CH:15]=[CH:14][N:13]=1.[H-].[Na+].Cl[C:27]1[CH:28]=[CH:29][C:30]2[N:31]([C:33]([N+:36]([O-:38])=[O:37])=[CH:34][N:35]=2)[N:32]=1.O>CN(C)C=O.O1CCCC1>[ClH:18].[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10][CH2:11][C:12]1[C:17]([Cl:18])=[C:16]([N:19]([CH3:23])[CH2:20][CH2:21][O:22][C:27]2[CH:28]=[CH:29][C:30]3[N:31]([C:33]([N+:36]([O-:38])=[O:37])=[CH:34][N:35]=3)[N:32]=2)[CH:15]=[CH:14][N:13]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 105359816-Chloro-3-nitro-imidazo(1,2-b)pyridazineHCID 187993912-{[2-(1H-benzimidazol-2-ylsulfanylmethyl)-3-chloropyridin-4-yl]-methylamino}-ethanol

Product 1

HCID 70272537[2-(1H-benzimidazol-2-ylsulfanylmethyl)-3-chloropyridin-4-yl]-methyl-[2-(3-nitroimidazo[1,2-b]pyridazin-6-yloxy)-ethyl]amine hydrochloride

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-{[2-(1H-benzimidazol-2-ylsulfanylmethyl)-3-chloropyridin-4-yl]-methylamino}-ethanol (7.5 g, 21.5 mmol) in dimethylformamide (75 ml) is treated with sodium hydride (1.4 g 80% strength suspension) and stirred for 1 h at room temperature. Then 6-chloro-3-nitro-imidazo[1,2-b]pyridazine (4.3 g, 21.5 mmol) in tetrahydrofurane (50 ml) is added dropwise over a period of 20 min and stirring is continued for another 2 h. The solution is treated with water (750 ml) and extracted extensively with ethyl acetate. The combined organic extracts are washed with water, dried over magnesium sulfate and evaporated in vacuo. The residue is chromatographed (silica, toluene/dioxane/ammonia 2:1:0.1) and crystallized from ethyl acetate. The crude product is dissolved in boiling 2-pronanol (250 ml) and treated with charcoal. After filtration and cooling to 35° C., a saturated solution of hydrogen chloride in diethyl ether (1.5 ml) is added and the mixture is cooled to 4° C. The precipitate is filtered, washed with 2-propanol and dried in vacuo to give the title compound as a faintly yellow solid, 3.6 g (31%). M.p. 211-2° C.

Workup

  1. stirringstirring
  2. waitis continued for another 2 h
  3. extractionextracted extensively with ethyl acetate
  4. washThe combined organic extracts are washed with water
  5. dry with materialdried over magnesium sulfate
  6. customevaporated in vacuo
  7. customThe residue is chromatographed (silica, toluene/dioxane/ammonia 2:1:0.1)
  8. customcrystallized from ethyl acetate
  9. dissolutionThe crude product is dissolved
  10. additiontreated with charcoal
  11. filtrationAfter filtration
  12. temperaturecooling to 35° C.
  13. additiona saturated solution of hydrogen chloride in diethyl ether (1.5 ml) is added
  14. temperaturethe mixture is cooled to 4° C
  15. filtrationThe precipitate is filtered
  16. washwashed with 2-propanol
  17. customdried in vacuo

Sources & evidence

ORD record
ord-cce0bea4d5544ed998ba69272ce369e0
Source dataset
uspto-grants-2000_03
Patent number
US06043242

Reaction notes

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