1,4-Dioxane → 6-[(4-Fluorophenyl)oxy]-N-methyl-N-(4-{[(3S)-3-methyl-1-piperazinyl]methyl}phenyl)-3-pyridinecarboxamide fumarate

HRID 534801Notes

Reaction equation

HRID 534801 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[N:14]=[CH:13][C:12]([C:15]([N:17]([CH3:32])[C:18]3[CH:23]=[CH:22][C:21]([CH2:24][N:25]4[CH2:30][CH2:29][NH:28][C@@H:27]([CH3:31])[CH2:26]4)=[CH:20][CH:19]=3)=[O:16])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[C:33]([OH:40])(=[O:39])/[CH:34]=[CH:35]/[C:36]([OH:38])=[O:37].O1CCOCC1>CC(CC(C)C)=O>[C:33]([OH:40])(=[O:39])/[CH:34]=[CH:35]/[C:36]([OH:38])=[O:37].[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[N:14]=[CH:13][C:12]([C:15]([N:17]([CH3:32])[C:18]3[CH:23]=[CH:22][C:21]([CH2:24][N:25]4[CH2:30][CH2:29][NH:28][C@@H:27]([CH3:31])[CH2:26]4)=[CH:20][CH:19]=3)=[O:16])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 444972Fumaric AcidHCID 237290236-[(4-Fluorophenyl)oxy]-N-methyl-N-(4-{[(3S)-3-methyl-1-piperazinyl]methyl}phenyl)-3-pyridinecarboxamide

Product 1

HCID 675263896-[(4-Fluorophenyl)oxy]-N-methyl-N-(4-{[(3S)-3-methyl-1-piperazinyl]methyl}phenyl)-3-pyridinecarboxamide fumarate

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent2×

Procedure

A solution of E2 free base (57.5 mg) in methyl iso-butylketone (0.5 mL) was added to fumaric acid (13.4 mg). Further methyl iso-butylketone (0.5 mL) was added and the mixture was heated with a hot air gun. The resulting yellow gum was scratched with a spatula and a small amount of white solid appeared throughout the gum. The sample was placed on a shaker block and temperature cycled (0-40° C. in 1 h blocks) over the weekend. To the resulting yellow gum in a colourless solution was added 1,4-dioxane (0.5 mL) and the mixture was heated to dissolve the gum. On cooling a gum formed and the sample was temperature cycled as before. After a period of ˜6 weeks a white solid slurry had formed. The mixture was placed back in the shaker block and temperature cycled as before, overnight. The mixture was then left to equilibrate to room temperature and the white solid was collected by filtration. After drying at 40° C. under vacuum overnight the title compound was obtained as a white, mainly crystalline powder (38.7 mg). M.pt. onset ˜150° C.

Workup

  1. temperaturethe mixture was heated with a hot air gun
  2. custom(0-40° C. in 1 h blocks)
  3. temperaturethe mixture was heated
  4. dissolutionto dissolve the gum
  5. temperatureOn cooling a gum
  6. customformed
  7. customAfter a period of ˜6 weeks a white solid slurry had formed
  8. customovernight
  9. waitThe mixture was then left
  10. customto equilibrate to room temperature
  11. filtrationthe white solid was collected by filtration
  12. dry with materialAfter drying at 40° C. under vacuum overnight the title compound

Sources & evidence

ORD record
ord-bd4bcc842bb94a249ddfee9ebd0638fd
Source dataset
uspto-grants-2014_10
Patent number
US08853218B2

Reaction notes

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