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

HRID 1067542노트

반응식

HRID 1067542 반응식
[H-].[Na+].[C:3]1([CH:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:10][CH:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][OH:20])[CH2:13][CH2:12]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:28]1[C:29]([CH3:46])=[CH:30][C:31]2[N:32]([CH:34]=[C:35]([C:37]([CH3:45])([CH3:44])[C:38]([O:40][CH:41]([CH3:43])[CH3:42])=[O:39])[N:36]=2)[N:33]=1>CN(C)C=O>[C:21]1([CH:9]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[O:10][CH:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][O:20][C:28]3[C:29]([CH3:46])=[CH:30][C:31]4[N:32]([CH:34]=[C:35]([C:37]([CH3:44])([CH3:45])[C:38]([O:40][CH:41]([CH3:42])[CH3:43])=[O:39])[N:36]=4)[N:33]=3)[CH2:13][CH2:12]2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 229892644-(Diphenylmethoxy)piperidinepropanolHCID 22989385Isopropyl 2-(6-chloro-7-methylimidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate

생성물 1

HCID 22989410Isopropyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propoxy)-7-methylimidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate수율 24.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To 10 ml of N,N-dimethylformamide, 0.16 g of a 60% dispersion of sodium hydride in mineral oil and 1.30 g of 4-(diphenylmethoxy)-1-piperidinepropanol were added, followed by stirring at room temperature under reduced pressure for 1 hour. While the reaction mixture was cooled with ice water, 1.31 g of isopropyl 2-(6-chloro-7methylimidazo[1,2-b]pyridazin-2-yl)-2-methylpropionate was added, followed by stirring at room temperature for 1.5 hours. To the reaction mixture, ice water 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 hexane:ethyl acetate (1:5). The desired fraction was collected to yield 582 mg of isopropyl 2-[6-[3-[4-(diphenylmethoxy)piperidino]propoxy]-7-methylimidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate as an oily substance. This oily substance was dissolved in 4 ml of ethanol; 2 ml of a 1 N aqueous solution of sodium hydroxide was added and reaction mixture was heated under reflux for 7 hours. After cooling, reaction mixture was concentrated under reduced pressure 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; the residue was crystallized by the addition of a small amount of water and ethyl ether, collected by filtration, washed with ethyl ether and dried to yield 0.413 g of the title compound.

후처리

  1. additionwas added
  2. stirringby stirring at room temperature for 1.5 hours
  3. extractionfollowed by extraction with ethyl acetate
  4. washthe extract was washed with saline
  5. dry with materialdried with magnesium sulfate
  6. concentrationThe dry product was concentrated under reduced pressure
  7. washeluted with hexane:ethyl acetate (1:5)
  8. customThe desired fraction was collected

출처 및 근거

ORD 기록
ord-afa3bfd19f174f3d997696cc0bcb096d
출처 데이터셋
uspto-grants-2001_06
특허 번호
US06248740B1

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