Dimethylformamide → 4-(4-(imidazo[1,2-b]pyridazin-6-ylmethoxy)phenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one

HRID 1842411ノート

反応式

HRID 1842411 の反応式
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:23])[C:10]([CH3:22])([CH3:21])[O:11][C:12]=2[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C.Cl[CH2:36][C:37]1[CH:38]=[CH:39][C:40]2[N:41]([CH:43]=[CH:44][N:45]=2)[N:42]=1>O>[N:45]1[CH:44]=[CH:43][N:41]2[C:40]=1[CH:39]=[CH:38][C:37]([CH2:36][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]3[C:9](=[O:23])[C:10]([CH3:21])([CH3:22])[O:11][C:12]=3[C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)=[CH:6][CH:7]=1)=[N:42]2

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 595801634-(4-hydroxyphenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-oneHCID 595801656-(Chloromethyl)imidazo[1,2-b]pyridazine

生成物 1

HCID 497789784-(4-(imidazo[1,2-b]pyridazin-6-ylmethoxy)phenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one収率 47.7%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
80 °C

実験手順

4-(4-Hydroxyphenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one (1.2 g, 3.8 mmol) was added to a mixture of cesium carbonate (3.7 g, 11.6 mmol) and DMF (25 mL) at RT under an atmosphere of nitrogen. The reaction mixture was stirred at RT for 30 min upon which 6-(chloromethyl)imidazo[1,2-b]pyridazine (0.96 g, 5 mmol) was added. The mixture was heated at 80° C. for 4 h (the reaction was monitored by TLC). The reaction mixture was diluted with water and extracted with EtOAc. The combined organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography using 30% ethyl acetate in n-hexane and silica gel (230-400 mesh) to afford 4-(4-(imidazo[1,2-b]pyridazin-6-ylmethoxy)phenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one (0.8 g, 47%,) as Off-white solid. 1H NMR: 200 MHz, DMSO-d6: δ 8.35 (s, 1H), 8.2 (d, 1H), 7.8 (s, 1H), 7.55 (d, 2H), 7.4 (d, 1H), 7.2 (d, 2H), 7.1 (d, 2H), 7.0 (d, 2H), 5.3 (s, 2H) 3.9 (s, 3H), 1.45 (s, 6H). MS: [M+H]+: m/z=442.1. HPLC: (95.8%, Condition-A).

後処理

  1. additionwas added
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash column chromatography

出典と根拠

ORDレコード
ord-2c5be53a048c419b9b299c8e42e9dbc5
出典データセット
uspto-grants-2015_02
特許番号
US08946222B2

反応ノート

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