Sodium Bicarbonate → 3-(1-(tert-Butyldimethylsilyloxy)-2-methylpropan-2-yl)-6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazine

HRID 1929977ノート

反応式

HRID 1929977 の反応式
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[CH2:24][CH2:23][CH2:22][N:12]2[C:13]=1[C:14]1[N:15]=[N:16][C:17]([NH:20][NH2:21])=[CH:18][CH:19]=1.[Si:25]([O:32][CH2:33][C:34]([CH3:38])([CH3:37])[CH:35]=O)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Si:25]([O:32][CH2:33][C:34]([C:38]1[N:16]2[N:15]=[C:14]([C:13]3[N:12]4[CH2:22][CH2:23][CH2:24][C:11]4=[N:10][C:9]=3[C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])[CH:19]=[CH:18][C:17]2=[N:20][N:21]=1)([CH3:37])[CH3:35])([C:28]([CH3:29])([CH3:30])[CH3:31])([CH3:26])[CH3:27]

参加物

6

反応物 4

HCID 516892Sodium BicarbonateHCID 106563753-((Tert-butyldimethylsilyl)oxy)-2,2-dimethylpropanalHCID 12217721Iodo benzene diacetateHCID 579298742-(2,4-Difluorophenyl)-3-(6-hydrazinylpyridazin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole

生成物 1

HCID 579299783-(1-(tert-Butyldimethylsilyloxy)-2-methylpropan-2-yl)-6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazine収率 90.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

2-(2,4-Difluorophenyl)-3-(6-hydrazinylpyridazin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (6.00 g, 18.3 mmol, Example #35, Step E) was suspended in DCM (125 μL) then 3-(tert-butyldimethylsilyloxy)-2,2-dimethylpropanal (4.15 g, 19.2 mmol, J. Org. Chem., 2002, 67, 2474-2480) was added. The mixture was stirred at ambient temperature for about 2 h. Iodobenzene diacetate (6.00 g, 18.6 mmol) was added then the mixture was stirred for about 30 min. Saturated aqueous NaHCO3 (150 mL) was added then the layers were separated. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The material was purified by flash chromatography on silica gel with EtOAc as an eluent to give the title compound (8.67 g, 90%): LC/MS (Table 1, Method g) Rt=2.77 min; MS m/z: 525.3.2 (M+H)+.

後処理

  1. stirringthe mixture was stirred for about 30 min
  2. customthe layers were separated
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe material was purified by flash chromatography on silica gel with EtOAc as an eluent

出典と根拠

ORDレコード
ord-dc01374e1f6a42bfb7a30abde210f0fa
出典データセット
uspto-grants-2012_05
特許番号
US08188083B2

反応ノート

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