Sodium Carbonate → 2-Methoxy-4-(6-methylimidazo[2,1-b][1,3,4]thiadiazol-2-yl)phenol

HRID 2409536Notes

Reaction equation

HRID 2409536 reaction equation
Br[C:2]1[S:6][C:5]2=[N:7][C:8]([CH3:10])=[CH:9][N:4]2[N:3]=1.[CH3:11][O:12][C:13]1[CH:18]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:16]=[CH:15][C:14]=1[OH:28].C([O-])([O-])=O.[Na+].[Na+]>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>[CH3:11][O:12][C:13]1[CH:18]=[C:17]([C:2]2[S:6][C:5]3=[N:7][C:8]([CH3:10])=[CH:9][N:4]3[N:3]=2)[CH:16]=[CH:15][C:14]=1[OH:28]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27346502-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 153575782-Bromo-6-methylimidazo[2,1-b][1,3,4]thiadiazole

Product 1

HCID 1363788042-Methoxy-4-(6-methylimidazo[2,1-b][1,3,4]thiadiazol-2-yl)phenol

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-bromo-6-methyl-imidazo[2,1-b][1,3,4]thiadiazole (1.53 g, 7.02 mmol, 1 eq) in dioxane (30 mL), 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (1.76 g, 7.02 mmol, 1 eq) was added followed by 2M aq. Na2CO3 (15 mL, 30 mmol, 4.3 eq). The suspension was degassed (N2, 15 min) and equipped with an argon balloon. Pd(Ph3P)2Cl2 (1.23 g, 1.75 mmol, 0.25 eq) was quickly added, and the reaction flask was placed in a pre-heated bath (115° C.). After stirring at reflux temperature for 2 h the reaction mixture was cooled to RT and concentrated. The residue was taken in water and extracted with DCM; the organic phase was washed with water, dried and concentrated to give 2-methoxy-4-(6-methylimidazo[2,1-b][1,3,4]thiadiazol-2-yl)phenol as a crude product (brown solid, 3 g) that was used in the next step without further purification. HPLC-MS (10-95% B in 4 min +2 min 100% B, flow 0.5 mL/min, 50° C.): tR=3.27 min, [M+H]+ m/z 262.0

Workup

  1. customThe suspension was degassed (N2, 15 min)
  2. customequipped with an argon balloon
  3. customthe reaction flask was placed in a pre-heated bath
  4. custom(115° C.)
  5. temperatureat reflux temperature for 2 h the reaction mixture
  6. concentrationconcentrated
  7. extractionextracted with DCM
  8. washthe organic phase was washed with water
  9. customdried
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-eaa601f4c8554cd49fa6c03c6395c680
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

Loading…