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

HRID 1169156Notes

Reaction equation

HRID 1169156 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.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>CS(C)=O.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

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 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 145.8%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

In 30 mL of dimethyl sulfoxide were suspended 18.18 g (56 mmol) of 4-(diphenylmethoxy)-1-piperidinepropaneamine, 10.00 g (37.4 mmol) of ethyl 2-(6-chloroimidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate and 7.92 g (74.7 mmol) of sodium carbonate, which were then heated to 130° C. under a nitrogen atmosphere and stirred for 9 hours. After cooling to room temperature, 100 mL of ethyl acetate and 100 mL of water were added, followed by separation into two layers. The organic layer was washed with 50 mL of water twice and concentrated under reduced pressure. To the residue was added 50 mL of ethanol and concentrated under reduced pressure to yield 30.3 g of crude ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate as an oily material (HPLC purity area percentage 58.3%). This oily material was dissolved in 70 mL of ethanol, and 2.99 g of sodium hydroxide dissolved in 30 mL of water was added thereto. The reaction mixture was heated to 60° C. and stirred for 1 hour. The reaction solution was concentrated under reduced pressure. To the residue were added 100 mL of water and 100 mL of ethyl acetate, followed by separation into two layers. The aqueous layer was washed with 50 mL of ethyl acetate twice, and 100 mL of ethanol was added to the aqueous layer. After the aqueous layer was adjusted to about pH 6 by the addition of 50 mL of 1N hydrochloric acid, the crystals formed were collected by filtration, washed with 40 mL of water and 40 mL of ethanol:water (1:1), and dried to yield 15.56 g of the title compound. HPLC purity area percentage 98.0%, Yield 72.3%.

Workup

  1. temperatureAfter cooling to room temperature
  2. customfollowed by separation into two layers
  3. washThe organic layer was washed with 50 mL of water twice
  4. concentrationconcentrated under reduced pressure
  5. additionTo the residue was added 50 mL of ethanol
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a4a3c232bbb141c88c8054dcf09d9da3
Source dataset
uspto-grants-2003_09
Patent number
US06627630B1

Reaction notes

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