Sodium Bicarbonate → Isopropyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino]-7-methylimidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate

HRID 1067543ノート

反応式

HRID 1067543 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[C:27]([CH3:44])=[CH:28][C:29]2[N:30]([CH:32]=[C:33]([C:35]([CH3:43])([CH3:42])[C:36]([O:38][CH:39]([CH3:41])[CH3:40])=[O:37])[N:34]=2)[N:31]=1.C(=O)(O)[O-].[Na+]>>[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[C:27]([CH3:44])=[CH:28][C:29]4[N:30]([CH:32]=[C:33]([C:35]([CH3:42])([CH3:43])[C:36]([O:38][CH:39]([CH3:40])[CH3:41])=[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

4

反応物 3

HCID 516892Sodium BicarbonateHCID 109693934-(Diphenylmethoxy)-1-piperidinepropaneamineHCID 22989385Isopropyl 2-(6-chloro-7-methylimidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate

生成物 1

HCID 22989370Isopropyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino]-7-methylimidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate収率 58.7%

実験手順

1.40 g of 4-(diphenylmethoxy)-1-piperidinepropanamine and 0.636 g of isopropyl 2-(6-chloro-7-methylimidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate were stirred at 190-200° C. for 3 hours. After cooling, aqueous sodium bicarbonate was added, followed by extraction with ethyl acetate; the extract was washed with saline and dried with magnesium sulfate. The dry product was concentrated under reduced pressure; the residue was subjected to silica gel column chromatography and eluted with ethyl acetate:methanol:triethylamine (185:15:2). The desired fraction was collected to yield 0.737 g of isopropyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propylamino]-7-methylimidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate as an oily substance. This oily substance was dissolved in 6 ml of ethanol; 3.15 ml of a 1 N aqueous solution of sodium hydroxide was added, followed by thermal refluxing for 7 hours. After cooling, the mixture was concentrated under reduced pressure; under ice cooling conditions, 1.89 ml of 1 N hydrochloric acid was added; the residue was washed with ethyl acetate. To the water layer, 1.89 ml of 1 N hydrochloric acid was added to saturate with sodium chloride, followed by extraction with ethyl acetate-tetrahydrofuran (1:1); the extract was washed with saturated saline and dried with magnesium sulfate. The dry product was concentrated under reduced pressure; 1.89 ml of 1 N hydrochloric acid was added to the residue, followed by concentration to dryness under reduced pressure; the residue was crystallized by the addition of ethyl ether, collected by filtration, washed with ethyl ether and dried to yield 0.445 g of the title compound.

後処理

  1. temperatureAfter cooling
  2. extractionfollowed by extraction with ethyl acetate
  3. washthe extract was washed with saline
  4. dry with materialdried with magnesium sulfate
  5. concentrationThe dry product was concentrated under reduced pressure
  6. washeluted with ethyl acetate:methanol:triethylamine (185:15:2)
  7. customThe desired fraction was collected

出典と根拠

ORDレコード
ord-a9690b1588f64e8aa6b16109cfd6e83f
出典データセット
uspto-grants-2001_06
特許番号
US06248740B1

反応ノート

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