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 1169163Notes

Reaction equation

HRID 1169163 reaction equation
[C:1]1([CH:7]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][NH:18][C:19]3[CH:20]=[CH:21][C:22]4[N:23]([CH:25]=[C:26]([C:28]([CH3:35])([CH3:34])[C:29]([O:31][CH2:32][CH3:33])=[O:30])[N:27]=4)[N:24]=3)[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.[C:43]([OH:55])(=[O:54])[CH2:44][C:45]([CH2:50][C:51]([OH:53])=[O:52])([C:47]([OH:49])=[O:48])[OH:46]>C(O)C>[C:43]([OH:55])(=[O:54])[CH2:44][C:45]([CH2:50][C:51]([OH:53])=[O:52])([C:47]([OH:49])=[O:48])[OH:46].[C:36]1([CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[O:8][CH:9]2[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][CH2:17][NH:18][C:19]3[CH:20]=[CH:21][C:22]4[N:23]([CH:25]=[C:26]([C:28]([CH3:35])([CH3:34])[C:29]([O:31][CH2:32][CH3:33])=[O:30])[N:27]=4)[N:24]=3)[CH2:13][CH2:14]2)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

4

Reactant 2

HCID 222302-Hydroxy-1,2,3-propanetricarboxylic acid hydrate (1:1)HCID 9872422Ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate

Product 1

HCID 69845596Ethyl 2-[6-[3-[4-(Diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate CitrateYield 89.5%

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 Reference Example 2C 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 still standing, the crystals formed were collected by filtration, washed with 10 mL of ethanol and dried to yield 2.007 g of the title compound.

Workup

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

Sources & evidence

ORD record
ord-bcccfe18f6dc434ebe3f4d61e8341091
Source dataset
uspto-grants-2003_09
Patent number
US06627630B1

Reaction notes

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