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

HRID 1169149ノート

反応式

HRID 1169149 の反応式
[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

参加物

7

反応物 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 109693934-(Diphenylmethoxy)-1-piperidinepropaneamineHCID 11043751Ethyl 2-(6-chloroimidazo[1,2-b]pyridazin-2-yl)-2-methylpropanoate

生成物 1

HCID 9872422Ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate収率 141.6%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒

反応条件

温度
167.5 °C

実験手順

In 600 mL of dimethyl sulfoxide were suspended 363.6 g (1120 mmol) of 4-(diphenylmethoxy)-1-piperidinepropaneamine, 200.0 g (747 mmol) of ethyl 2-(6-chloroimidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate and 158.4 g (1490 mmol) of sodium carbonate, which were then heated in an oil bath (bath temperature 165-170° C.) under a nitrogen gas stream and stirred for 3.5 hours. After cooling to room temperature, 2000 mL of ethyl acetate and 2000 mL of water were added, followed by separation into two layers. The organic layer was washed with 1000 mL of water twice and concentrated under reduced pressure. To the residue was added 1000 mL of ethanol and concentrated under reduced pressure to yield 588 g of crude ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate as an oily material. This oily material was dissolved in 1400 mL of ethanol, and 59.8 g (1490 mmol) of sodium hydroxide dissolved in 600 mL of water was added thereto. The reaction mixture was heated to 60° C. (inner temperature) and stirred for 1 hour. The reaction solution was concentrated under reduced pressure. To the residue were added 2000 mL of water and 2000 mL of ethyl acetate, followed by separation into two layers. The aqueous layer was washed with 1000 mL of ethyl acetate twice, and 2000 mL of ethanol was added to the aqueous layer. After the aqueous layer was adjusted to about pH 6 by the addition of 1000 mL of 1N hydrochloric acid, the crystals formed were collected by filtration, washed with 800 mL of water and 800 mL of ethanol:water (1:1), and dried to yield 353.6 g of the crude title compound. HPLC purity area percentage 97.7%, Yield 82.0%.

後処理

  1. temperatureAfter cooling to room temperature
  2. customfollowed by separation into two layers
  3. washThe organic layer was washed with 1000 mL of water twice
  4. concentrationconcentrated under reduced pressure
  5. additionTo the residue was added 1000 mL of ethanol
  6. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-df83d333c6b1479298e044ad507c09de
出典データセット
uspto-grants-2003_09
特許番号
US06627630B1

反応ノート

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