Dimethylformamide → HCID 49778979, compound

HRID 1798700Notes

Reaction equation

HRID 1798700 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)[N: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)[N:41]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 109655626-chloro-2-(chloromethyl)imidazo[1,2-b]pyridazineHCID 595801634-(4-hydroxyphenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one

Product 1

HCID 49778979HCID 49778979, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

4-(4-Hydroxyphenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one (200 mg, 0.64 mmol) was added to a mixture of cesium carbonate (838 mg, 2.5 mmol) and DMF (5 mL) at RT under an atmosphere of nitrogen. The reaction mixture was stirred at RT for 30 min upon which 6-chloro-2-(chloromethyl) imidazo[1,2-b]pyridazine (196 mg, 9.6 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 organic residue was purified by flash column chromatography using 30% ethyl acetate in n-hexane and silica gel (230-400 mesh) to afford 4-(4-((6-chloroimidazo[1,2-b]pyridazin-2-yl)methoxy)phenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one (180 mg, 63.0%) as an off-white solid. 1H NMR, 500 MHz, DMSO-d6: δ 8.45 (s, 1H), 8.2 (d, 1H), 7.55 (d, 2H), 7.4 (d, 1H), 7.15 (d, 2H), 7.1 (d, 2H), 7.0 (d, 2H), 5.25 (s, 2H), 3.8 (s, 3H), 1.25 (s, 6H). MS: [M+H]+: m/z=476.7. HPLC: (96.7%, Condition-A).

Workup

  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 organic residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-d71ba9ba69474d929e11ac5fcd803af1
Source dataset
uspto-grants-2013_01
Patent number
US08343973B2

Reaction notes

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