Sodium Carbonate → 2-(3,4-Dimethoxy-phenyl)-imidazo[2,1-b][1,3,4]thiadiazole

HRID 2409550Notes

Reaction equation

HRID 2409550 reaction equation
Br[C:2]1[S:6][C:5]2=[N:7][CH:8]=[CH:9][N:4]2[N:3]=1.[CH3:10][O:11][C:12]1[CH:13]=[C:14](B(O)O)[CH:15]=[CH:16][C:17]=1[O:18][CH3:19].O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=O.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>[CH3:10][O:11][C:12]1[CH:13]=[C:14]([C:2]2[S:6][C:5]3=[N:7][CH:8]=[CH:9][N:4]3[N:3]=2)[CH:15]=[CH:16][C:17]=1[O:18][CH3:19]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 27347023,4-Dimethoxyphenylboronic acidHCID 436679232-Bromoimidazo[2,1-b][1,3,4]thiadiazole

Product 1

HCID 667170372-(3,4-Dimethoxy-phenyl)-imidazo[2,1-b][1,3,4]thiadiazoleYield 12.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 2-bromo-imidazo[2,1-b][1,3,4]thiadiazole (0.5 g, 2.5 mmol, 1 eq), 3,4-dimethoxyphenylboronic acid (0.683 g, 3.7 mmol, 1.5 eq), dioxane (12.5 mL) and Na2CO3 (2M aq. solution, 3.8 mL) was degassed for 20 minutes at room temperature. Pd(Ph3P)2Cl2 was added and the reaction heated at 110° C. for 2 h in an argon atmosphere. The reaction mixture was diluted with EtOAc and washed with water. The combined organic layers were dried (Na2SO4), filtered and concentrated, and the residue was purified by column chromatography (SiO2, cyclohexane/20-100% ethylacetate). The product was further purified by triturating with Et2O, filtered off and dried affording the desired product (0.080 g). 1H NMR (300 MHz, DMSO) δ/ppm 8.18 (d, J=1.4, 1H), 7.47 (m, 2H), 7.33 (d, J=1.4, 1H), 7.15 (d, J=8.3, 1H), 3.86 (s, 3H), 3.75 (s, 3H). The filtrate was concentrated, redissolved in DCM and purified by flash-chromatography (SiO2, DCM/1% MeOH) to afford the desired product (0.65 g, containing some Ph3PO) that was used as such in the next step.

Workup

  1. washwashed with water
  2. dry with materialThe combined organic layers were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customthe residue was purified by column chromatography (SiO2, cyclohexane/20-100% ethylacetate)
  6. customThe product was further purified
  7. customby triturating with Et2O
  8. filtrationfiltered off
  9. customdried

Sources & evidence

ORD record
ord-3313ddb75cb9412e851528677ded68c7
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

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