Water → HCID 22989256, compound

HRID 1169165Notes

Reaction equation

HRID 1169165 reaction equation
[C:1]1([CH:7]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][NH2:18])[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:26]1[CH:27]=[CH:28][C:29]2[N:30]([C:32]([CH3:43])=[C:33]([C:35]([CH3:42])([CH3:41])[C:36]([O:38][CH2:39][CH3:40])=[O:37])[N:34]=2)[N:31]=1.O>CN1CCCC1=O>[C:19]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][NH:18][C:26]3[CH:27]=[CH:28][C:29]4[N:30]([C:32]([CH3:43])=[C:33]([C:35]([CH3:42])([CH3:41])[C:36]([O:38][CH2:39][CH3:40])=[O:37])[N:34]=4)[N:31]=3)[CH2:11][CH2:10]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 962WaterHCID 109693934-(Diphenylmethoxy)-1-piperidinepropaneamineHCID 22989317HCID 22989317, compound

Product 1

HCID 22989256HCID 22989256, compoundYield 69.6%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
160 °C

Procedure

In 25 mL of N-methyl-2-pyrrolidinone were dissolved 17.0 g of 4-(diphenylmethoxy)-1-piperidinepropaneamine and 7.39 g of ethyl 2-(6-chloro-3-methylimidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate, and stirred at 160° C. for 8.5 hours. After cooling, a water was added and extracted with ethyl acetate. The extract was washed with a saturated brine solution and dried over magnesium sulfate. Following to concentration under reduced pressure. The residue was subjected to silica gel column chromatography to be eluted with ethyl acetate:methanol:triethylamine (50:5:1). The desired fraction was collected and concentrated to yield 10.4 g of ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino]-3-methylimidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate as an oily material. In 100 mL of ethanol was dissolved this oily material, and 18.3 mL of a 5N aqueous sodium hydroxide solution was added thereto and heated under reflux for 2 hours. After cooling, the mixture was concentrated under reduced pressure. The residue was diluted with water and washed with diisopropyl ether. The aqueous layer was adjusted to pH 5 by the addition of 5N hydrochloric acid. The crystals formed were collected by filtration, recrystallized from methanol-water (10:1), and dried to yield 4.09 g (of the title compound.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with a saturated brine solution
  4. dry with materialdried over magnesium sulfate
  5. concentrationFollowing to concentration under reduced pressure
  6. washto be eluted with ethyl acetate:methanol:triethylamine (50:5:1)
  7. customThe desired fraction was collected
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-6bfbd6c1397f4859a37333efd7c3d0d4
Source dataset
uspto-grants-2003_09
Patent number
US06627630B1

Reaction notes

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