Dimethylformamide → 4-(4-((6-chloroimidazo[1,2-a]pyridin-2-yl)methoxy)phenyl)-5-(4-methoxy phenyl)-2,2-dimethylfuran-3(2H)-one

HRID 1842435Notes

Reaction equation

HRID 1842435 reaction equation
[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:35][C:36]1[CH:37]=[CH:38][C:39]2[N:40]([CH:42]=[C:43]([CH2:45]Cl)[N:44]=2)[CH:41]=1>O>[Cl:35][C:36]1[CH:37]=[CH:38][C:39]2[N:40]([CH:42]=[C:43]([CH2:45][O:1][C:2]3[CH:3]=[CH:4][C:5]([C:8]4[C:9](=[O:23])[C:10]([CH3:21])([CH3:22])[O:11][C:12]=4[C:13]4[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=4)=[CH:6][CH:7]=3)[N:44]=2)[CH:41]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 48683896-Chloro-2-(chloromethyl)imidazo[1,2-a]pyridineHCID 595801634-(4-hydroxyphenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one

Product 1

HCID 497796644-(4-((6-chloroimidazo[1,2-a]pyridin-2-yl)methoxy)phenyl)-5-(4-methoxy phenyl)-2,2-dimethylfuran-3(2H)-oneYield 39.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

4-(4-Hydroxyphenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one (300 mg, 0.96 mmol) was added to a mixture of cesium carbonate (1.05 g, 3.8 mmol) and DMF (20 mL) at RT under nitrogen. The reaction mixture was stirred at RT for 30 minutes, upon which 6-chloro-2-(chloromethyl)imidazo[1,2-a]pyridine (201 mg, 1.4 mmol) was added. The mixture was heated at 80° C. for 4 h (the reaction was monitored by TLC). Upon completion of the reaction as judged 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 20% ethyl acetate in n-hexane and silica gel (230-400 mesh) to afford 4-(4-((6-chloroimidazo[1,2-a]pyridin-2-yl)methoxy)phenyl)-5-(4-methoxy phenyl)-2,2-dimethylfuran-3(2H)-one (180 mg, 39.3%,) as a white solid. 1H NMR, 500 MHz, DMSO-d6: δ 8.85 (s, 1H), 8.0 (s, 1H), 7.6 (d, 3H), 7.3 (d, 1H), 7.15 (d, 2H), 7.1 (d, 2H), 7.0 (d, 2H), 5.15 (s, 2H) 3.8 (s, 3H), 1.4 (s, 6H). MS: [M+H]+: m/z=475. HPLC: (98.0%, Condition-A).

Workup

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

Sources & evidence

ORD record
ord-1068260542b640eb909fd8708a23353f
Source dataset
uspto-grants-2015_02
Patent number
US08946222B2

Reaction notes

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