Methanol → HCID 69524646, compound

HRID 350700Notes

Reaction equation

HRID 350700 reaction equation
[F:1][C:2]1[CH:27]=[CH:26][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][NH:17][C:18]4[CH:23]=[N:22][NH:21][C:20](=[O:24])[C:19]=4[Cl:25])[CH2:11][CH2:10]3)=N[O:8][C:4]=2[CH:3]=1.C[OH:29].[OH-].[Na+].[H][H]>[Pd].ClCCl>[ClH:25].[ClH:25].[F:1][C:2]1[CH:27]=[CH:26][C:5]([C:6]([CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][NH:17][C:18]3[CH:23]=[N:22][NH:21][C:20](=[O:24])[CH:19]=3)[CH2:11][CH2:10]2)=[O:29])=[C:4]([OH:8])[CH:3]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 21973237HCID 21973237, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 69524646HCID 69524646, compoundYield 50.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent

Procedure

Into a pressure-tight hydrogenating apparatus 3.5 g (0.009 mole) of 5-{2-[4-(6-fluoro-1,2-benzisoxazole-3-yl)-piperidine-1-yl]-ethylamino}-4-chloro-2H-pyridazine-3-one, 350 ml of a solvent mixture (1:1 mixture of methanol and dichloro methane), 0.4 g (0.01 mole) of sodium hydroxide and 7 g of a palladium charcoal catalyst (composition: 8% of palladium, 28% of carbon, 64% of water) are weighed in. The reaction mixture is stirred at a hydrogen pressure of 10 atm. for 16 hours. Hydrogen is removed from the apparatus. The reaction mixture is heated to reflux temperature and stirred at this temperature for 5 minutes. The mixture is filtered hot and the catalyst is washed five times with 350 ml of a 1:1 mixture of methanol and dichloro methane each. The united mother-lyes are evaporated in vacuo. The crude product is dissolved in a 9:1 mixture of 2-propanol and water under stirring and reflux, filtered and the filtrate is evaporated to 100 ml. The mixture is stirred under cooling with icecold water for half an hour. The precipitated crystals are filtered, suspended in a 9:1 mixture of 2-propanol and water and the suspension is acidified by adding concentrated aqueous hydrochloric acid. To the suspension under reflux a 9:1 mixture of 2-propanol and water is added until a clear solution is obtained. The solution is filtered warm, the filtrate is evaporated to 15 ml, the concentrate is stirred under cooling with icecold water and the crystals are filtered off. Thus 1.95 g of the desired compound are obtained. Yield 50.4%. M.p.: 267–269° C.

Workup

  1. customHydrogen is removed from the apparatus
  2. temperatureThe reaction mixture is heated
  3. temperatureto reflux temperature
  4. filtrationThe mixture is filtered hot
  5. washthe catalyst is washed five times
  6. additionwith 350 ml of a 1:1 mixture of methanol and dichloro methane each
  7. customThe united mother-lyes are evaporated in vacuo
  8. dissolutionThe crude product is dissolved in a 9:1 mixture of 2-propanol and water
  9. stirringunder stirring
  10. temperaturereflux
  11. filtrationfiltered
  12. customthe filtrate is evaporated to 100 ml
  13. stirringThe mixture is stirred
  14. temperatureunder cooling with icecold water for half an hour
  15. filtrationThe precipitated crystals are filtered
  16. additionsuspended in a 9:1 mixture of 2-propanol and water
  17. additionby adding concentrated aqueous hydrochloric acid
  18. temperatureTo the suspension under reflux
  19. additiona 9:1 mixture of 2-propanol and water
  20. additionis added until a clear solution
  21. customis obtained
  22. filtrationThe solution is filtered
  23. temperaturewarm
  24. customthe filtrate is evaporated to 15 ml
  25. stirringthe concentrate is stirred
  26. temperatureunder cooling with icecold water
  27. filtrationthe crystals are filtered off

Sources & evidence

ORD record
ord-203d9a25f189438892bce52b3a88389c
Source dataset
uspto-grants-2007_02
Patent number
US07183283B2

Reaction notes

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