Water → Ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate

HRID 1169153Notes

Reaction equation

HRID 1169153 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]([CH:32]=[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.C(=O)([O-])O.[Na+]>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]([CH:32]=[C:33]([C:35]([CH3:41])([CH3:42])[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

6

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 109693934-(Diphenylmethoxy)-1-piperidinepropaneamineHCID 11043751Ethyl 2-(6-chloroimidazo[1,2-b]pyridazin-2-yl)-2-methylpropanoate

Product 1

HCID 9872422Ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionateYield 92.5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
193 °C

Procedure

In 13.4 mL of N-methyl-2-pyrrolidinone were dissolved 6.49 g (20 mmol) of 4-(diphenylmethoxy)-1-piperidinepropaneamine and 2.68 g (10.0 mmol) of ethyl 2-(6-chloroimidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate, heated to 191-195° C. under a nitrogen atmosphere and stirred for 4.5 hours. After cooling to room temperature, 20 mL of water and 1.01 g (2 mmol) of sodium hydrogencarbonate were added and extracted twice with 30 mL of ethyl acetate. The extract was washed with 20 mL of water three times and the organic layer was concentrated under reduced pressure. The residue was subjected to silica gel chromatography to be eluted with ethyl acetate:methanol:triethylamine (100:5:1). The desired fraction was collected and concentrated to provide 5.14 g of the crude title compound. Purity 83%, yield 77%, determined from the integral values of the proton NMR.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted twice with 30 mL of ethyl acetate
  3. washThe extract was washed with 20 mL of water three times
  4. concentrationthe organic layer was concentrated under reduced pressure
  5. washto be eluted with ethyl acetate:methanol:triethylamine (100:5:1)
  6. customThe desired fraction was collected
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-98d70c82110044d4869519367f844c45
Source dataset
uspto-grants-2003_09
Patent number
US06627630B1

Reaction notes

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