3-Hydroxy-3-methyl-butanal → 1-(6-(6-(2,4-Difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)-2-methylpropan-2-ol

HRID 1930095ノート

反応式

HRID 1930095 の反応式
[OH:1][C:2]([CH3:7])([CH3:6])[CH2:3][CH:4]=O.[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C:16]1[N:17]=[C:18]2[N:22]([C:23]=1[C:24]1[N:25]=[N:26][C:27]([NH:30][NH2:31])=[CH:28][CH:29]=1)[CH:21]=[CH:20][O:19]2.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1>C(Cl)Cl>[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C:16]1[N:17]=[C:18]2[N:22]([C:23]=1[C:24]1[CH:29]=[CH:28][C:27]3[N:26]([C:4]([CH2:3][C:2]([CH3:7])([OH:1])[CH3:6])=[N:31][N:30]=3)[N:25]=1)[CH:21]=[CH:20][O:19]2

参加物

5

反応物 3

HCID 110515913-Hydroxy-3-methyl-butanalHCID 12217721Iodo benzene diacetateHCID 579298696-(2,4-Difluorophenyl)-5-(6-hydrazinylpyridazin-3-yl)imidazo[2,1-b]oxazole

生成物 1

HCID 498308011-(6-(6-(2,4-Difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)-2-methylpropan-2-ol収率 33.5%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To round bottom flask, 3-hydroxy-3-methylbutanal (0.178 g, 1.185 mmol) and 6-(2,4-difluorophenyl)-5-(6-hydrazinylpyridazin-3-yl)imidazo[2,1-b]oxazole (0.3 g, 0.859 mmol) and DCM 5 mL were added. The reaction mixture was stirred at about ambient temperature for about 1 h. Iodobenzene diacetate (0.38 g, 1.18 mmol) was added and was stirred at ambient temperature for overnight. The reaction mixture was quenched with water. The aqueous phase was extracted with DCM and the organic layer was concentrated under reduced pressure. The crude material was purified by silica gel chromatography using DCM/MeOH (90:10). After concentration of the fractions with product, the resulting solid was triturated with ether. The solid was collected by filtration then dried under vacuum at about 60° C. for about 2 days to give the title compound (0.118 g, 33.5%): LC/MS (Table 1, Method g) Rt=1.78 min; MS m/z: 411.2 (M+H)+. 1H NMR (DMSO-d6) δ 8.52 (d, 1H), 8.27 (d, 1H), 8.21 (d, 1H), 7.75 (m, 1H), 7.50-7.40 (m, 1H), 7.34-7.25 (m, 1H), 6.90 (m, 1H), 4.71 (s, 1H), 3.33 (s, 2H), 1.27 (s, 6H)

後処理

  1. stirringwas stirred at ambient temperature for overnight
  2. customThe reaction mixture was quenched with water
  3. extractionThe aqueous phase was extracted with DCM
  4. concentrationthe organic layer was concentrated under reduced pressure
  5. customThe crude material was purified by silica gel chromatography
  6. customAfter concentration of the fractions with product, the resulting solid was triturated with ether
  7. filtrationThe solid was collected by filtration
  8. customthen dried under vacuum at about 60° C. for about 2 days

出典と根拠

ORDレコード
ord-23f8338d970d4a7285caf64f16efb392
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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