Water → {3-[2-(4-Fluoro-phenoxy)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-phenyl}-dimethyl-amine

HRID 1043657Notes

Reaction equation

HRID 1043657 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.[CH3:18][N:19]([C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[CH:25][CH:26]=1)[CH3:20].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>[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]=[C:21]([N:19]([CH3:20])[CH3:18])[CH:22]=[CH:23][CH:24]=4)[N:9]3[N:8]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27625273-(Dimethylamino)benzeneboronic acidHCID 673357762-(4-Fluoro-phenoxy)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole

Product 1

HCID 67334588{3-[2-(4-Fluoro-phenoxy)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-phenyl}-dimethyl-amineYield 10.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

2-(4-Fluoro-phenoxy)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole (0.13 g, 0.36 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) (42 mg, 0.036 mmol), 3-(N,N-dimethylamino)phenylboronic acid (68 mg, 0.41 mmol), cesium carbonate (235 mg, 0.72 mmol, 2.0 eq), and water (1.5 mL) were added. The mixture was deoxygenated for 10 minutes and heated under microwave irradiation at 140° C. for 1 hour. 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 2:8). The obtained residue was crystallized from methanol:1,2-dichloroethane (1:1, 1.5 mL) and filtered to give {3-[2-(4-fluoro-phenoxy)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-phenyl}-dimethyl-amine as a white solid (13 mg, 10% 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 2:8)
  6. customThe obtained residue was crystallized from methanol:1,2-dichloroethane (1:1, 1.5 mL)
  7. filtrationfiltered

Sources & evidence

ORD record
ord-0f480f0039464fc79a0b45bbd09b6e48
Source dataset
uspto-grants-2013_10
Patent number
US08563550B2

Reaction notes

Loading…