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

HRID 1798697노트

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HRID 1798697 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 962Water용매

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온도
80 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-c21a1873fbbb47159aeaa9241c38cb76
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08343973B2

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