2-Hydroxy-1,2,3-propanetricarboxylic acid hydrate (1:1) → Ethyl 2-[6-[3-[4-(Diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate Citrate

HRID 1169148Notes

Reaction equation

HRID 1169148 reaction equation
C(O)(=O)/C=C/C(O)=O.C(O)(=O)/C=C/C(O)=O.[C:17]1([CH:23]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[O:24][CH:25]2[CH2:30][CH2:29][N:28]([CH2:31][CH2:32][CH2:33][NH:34][C:35]3[CH:36]=[CH:37][C:38]4[N:39]([CH:41]=[C:42]([C:44]([CH3:51])([CH3:50])[C:45]([O:47][CH2:48][CH3:49])=[O:46])[N:43]=4)[N:40]=3)[CH2:27][CH2:26]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.O.[C:59]([OH:71])(=[O:70])[CH2:60][C:61]([CH2:66][C:67]([OH:69])=[O:68])([C:63]([OH:65])=[O:64])[OH:62]>C(O)C>[C:59]([OH:71])(=[O:70])[CH2:60][C:61]([CH2:66][C:67]([OH:69])=[O:68])([C:63]([OH:65])=[O:64])[OH:62].[C:52]1([CH:23]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:24][CH:25]2[CH2:26][CH2:27][N:28]([CH2:31][CH2:32][CH2:33][NH:34][C:35]3[CH:36]=[CH:37][C:38]4[N:39]([CH:41]=[C:42]([C:44]([CH3:51])([CH3:50])[C:45]([O:47][CH2:48][CH3:49])=[O:46])[N:43]=4)[N:40]=3)[CH2:29][CH2:30]2)[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1

Participants

4

Reactant 2

HCID 222302-Hydroxy-1,2,3-propanetricarboxylic acid hydrate (1:1)HCID 69842492Ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino] propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate difumarate

Product 1

HCID 69845596Ethyl 2-[6-[3-[4-(Diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate CitrateYield 127%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

In 8 mL of ethanol, 1.667 g of the ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate synthesized in Example 40A was dissolved, and 0.631 g of citric acid monohydrate was added thereto and dissolved under heating, followed by concentration under reduced pressure. To the residue was added 23 mL of ethyl acetate, and the crystals formed were collected by filtration and washed with 12 mL of ethyl acetate. To the crystals was added 30 mL of methanol and the crystals were dissolved under heating, followed by concentration under reduced pressure. To the residue was added 30 mL of ethanol and the residue was then dissolved. After standing, the crystals formed were collected by filtration, washed with 10 mL of ethanol and dried to yield 2.01 g of the title compound.

Workup

  1. dissolutiondissolved
  2. temperatureunder heating
  3. concentrationfollowed by concentration under reduced pressure
  4. additionTo the residue was added 23 mL of ethyl acetate
  5. customthe crystals formed
  6. filtrationwere collected by filtration
  7. washwashed with 12 mL of ethyl acetate
  8. additionTo the crystals was added 30 mL of methanol
  9. dissolutionthe crystals were dissolved
  10. temperatureunder heating
  11. concentrationfollowed by concentration under reduced pressure
  12. additionTo the residue was added 30 mL of ethanol
  13. dissolutionthe residue was then dissolved
  14. customthe crystals formed
  15. filtrationwere collected by filtration
  16. washwashed with 10 mL of ethanol
  17. customdried

Sources & evidence

ORD record
ord-a5a26828a13e48ae81b237e5f89052e3
Source dataset
uspto-grants-2003_09
Patent number
US06627630B1

Reaction notes

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