Sodium Hydroxide → 3-Chloro-6-{[2-(piperidin-1-yl)ethyl]sulfanyl}pyridazine

HRID 1439157Notes

Reaction equation

HRID 1439157 reaction equation
[NH2:1][C:2](N)=[S:3].Cl[CH2:6][CH2:7][N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1.[OH-].[Na+].[Cl:16][C:17]1[N:18]=NC(Cl)=[CH:21][CH:22]=1>C(O)C.O.[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.C1(C)C=CC=CC=1>[Cl:16][C:17]1[N:18]=[N:1][C:2]([S:3][CH2:6][CH2:7][N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:21][CH:22]=1

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 673313,6-DichloropyridazineHCID 748271-(2-Chloroethyl)piperidineHCID 2723790Thiourea

Product 1

HCID 227677953-Chloro-6-{[2-(piperidin-1-yl)ethyl]sulfanyl}pyridazine

Reagents, catalysts & solvents 4

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a warm, stirred solution of 11.4 g (0.150 mole) of thiourea in 175 ml of ethanol was added 22.1 g (0.150 mole) of 1-(2-chloroethyl)piperidine. The resulting solution was heated under reflux for 4 hours. The ethanol was then removed by evaporation in vacuo, and the semisolid residue was taken up in a solution of 12.0 g (0.300 mole) of sodium hydroxide in 180 ml of water. The solution, thus prepared, was added with vigorous stirring to a solution of 22.2 g (0.149 mole) of 3,6-dichloropyridazine and 0.53 g of benzyltriethylammonium chloride in 500 ml of toluene. The mixture was heated under reflux with vigorous stirring for 2 hours, after which period of time the mixture was cooled to room temperature, and the toluene phase was separated. The aqueous phase was extracted with one portion of toluene, and the extract was added to the said toluene phase. The toluene solution, thus obtained, was dried over anhydrous sodium sulfate, filtered and the toluene was removed from the filtrate by evaporation in vacuo. The solid residue was recrystallized from propanol-2 to give 27.3 (71%) of the 3-chloro-6-(2-(1-piperidinyl)ethylthio)pyridazine as white, fibrous crystals. The product was found to melt at 103.5 to 104° C and to have carbon, hydrogen, and nitrogen contents of 51.3%, 6.21%, and 16.36%, respectively, as compared to theoretical contents of 51.25%, 6.26%, and 16.30%.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureunder reflux for 4 hours
  3. customThe ethanol was then removed by evaporation in vacuo
  4. customThe solution, thus prepared
  5. additionwas added
  6. temperatureThe mixture was heated
  7. temperatureunder reflux
  8. customthe toluene phase was separated
  9. extractionThe aqueous phase was extracted with one portion of toluene
  10. additionthe extract was added to the said toluene phase
  11. customThe toluene solution, thus obtained
  12. dry with materialwas dried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. customthe toluene was removed from the filtrate by evaporation in vacuo
  15. customThe solid residue was recrystallized from propanol-2

Sources & evidence

ORD record
ord-aee4693f58a34d74855537dd83a7e0d8
Source dataset
uspto-grants-1977_11
Patent number
US04058520

Reaction notes

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