Water → N-{4-[2-(4-fluoro-phenoxy)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-phenyl}-acetamide

HRID 1043659Notes

Reaction equation

HRID 1043659 reaction equation
[F:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[S:11][C:10]3=[N:12][CH:13]=[C:14](I)[N:9]3[N:8]=2)=[CH:4][CH:3]=1.[C:18]([NH:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)(=[O:20])[CH3:19].C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)C>[F:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[S:11][C:10]3=[N:12][CH:13]=[C:14]([C:25]4[CH:26]=[CH:27][C:22]([NH:21][C:18](=[O:20])[CH3:19])=[CH:23][CH:24]=4)[N:9]3[N:8]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27346574-Acetamidophenylboronic acidHCID 673357762-(4-Fluoro-phenoxy)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole

Product 1

HCID 67335431N-{4-[2-(4-fluoro-phenoxy)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-phenyl}-acetamideYield 43%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

2-(4-Fluoro-phenoxy)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole (0.15 g, 0.42 mmol) was suspended in 1,4-dioxane (1.5 mL) at room temperature and argon was bubbled into the mixture while dichlorobis(triphenylphosphine)palladium(II) (29 mg, 0.042 mmol), 4-acetamidophenylboronic acid (85 mg, 0.48 mmol), cesium carbonate (271 mg, 0.83 mmol) and water (1.5 mL) were added. The mixture was deoxygenated for 10 minutes and heated under microwave irradiation at 140° C. for 20 minutes. On cooling, the resulting suspension was diluted with dichloromethane (7 mL), adsorbed in silica and purified by column chromatography (Biotage™/Flash, silica, methanol:dichloromethane 0.2:9.8 to 2:8). The residue obtained was treated with diethylether (7 mL) and filtered to give 66 mg of N-{4-[2-(4-fluoro-phenoxy)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-phenyl}-acetamide as a white solid (43%).

Workup

  1. additionwere added
  2. customThe mixture was deoxygenated for 10 minutes
  3. temperatureOn cooling
  4. additionthe resulting suspension was diluted with dichloromethane (7 mL)
  5. custompurified by column chromatography (Biotage™/Flash, silica, methanol:dichloromethane 0.2:9.8 to 2:8)
  6. customThe residue obtained
  7. filtrationfiltered

Sources & evidence

ORD record
ord-f7536b47433241f3b5a7a25400d8c874
Source dataset
uspto-grants-2013_10
Patent number
US08563550B2

Reaction notes

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