Water → 4-[2-(4-Fluoro-phenoxy)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-phenol

HRID 1043658Notes

Reaction equation

HRID 1043658 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.[OH:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.ClCCl>[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:22]4[CH:23]=[CH:24][C:19]([OH:18])=[CH:20][CH:21]=4)[N:9]3[N:8]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27343604-Hydroxyphenylboronic acidHCID 673357762-(4-Fluoro-phenoxy)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole

Product 1

HCID 673343104-[2-(4-Fluoro-phenoxy)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-phenolYield 27%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 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 tetrakis(triphenylphosphine)palladium(0) (48 mg, 0.042 mmol), 4-hydroxyphenylboronic acid (66 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 mixture was diluted with dichloromethane (7 mL), adsorbed in silica and purified by column chromatography (Biotage™/Flash, silica, methanol:dichloromethane 0.2:9.8 to 1.5:7.5). The product obtained was treated with dichloromethane (5 mL) and filtered to give 4-[2-(4-fluoro-phenoxy)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-phenol as a white solid (37 mg, 27% yield).

Workup

  1. additionwere added
  2. customThe mixture was deoxygenated for 10 minutes
  3. temperatureOn cooling
  4. additionthe mixture was diluted with dichloromethane (7 mL)
  5. custompurified by column chromatography (Biotage™/Flash, silica, methanol:dichloromethane 0.2:9.8 to 1.5:7.5)
  6. customThe product obtained
  7. filtrationfiltered

Sources & evidence

ORD record
ord-b6f5612227384747a28c3e8261a7c500
Source dataset
uspto-grants-2013_10
Patent number
US08563550B2

Reaction notes

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