Nitrogen → 2,5-bis(4-(5-methylthiophen-2-yl)-1H-imidazol-2-yl)thiophene

HRID 1429113Notes

Reaction equation

HRID 1429113 reaction equation
I[C:2]1[NH:3][CH:4]=[C:5]([C:7]2[S:8][C:9]([CH3:12])=[CH:10][CH:11]=2)[N:6]=1.[S:13]1[C:17](B(O)O)=[CH:16][CH:15]=[C:14]1B(O)O.C([O-])([O-])=O.[Na+].[Na+].N#N>O.CN(C=O)C.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>[CH3:12][C:9]1[S:8][C:7]([C:5]2[N:6]=[C:2]([C:14]3[S:13][C:17]([C:2]4[NH:3][CH:4]=[C:5]([C:7]5[S:8][C:9]([CH3:12])=[CH:10][CH:11]=5)[N:6]=4)=[CH:16][CH:15]=3)[NH:3][CH:4]=2)=[CH:11][CH:10]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 27709062,5-Thiophenediylbisboronic acidHCID 178423882HCID 178423882, compound

Product 1

HCID 1784238782,5-bis(4-(5-methylthiophen-2-yl)-1H-imidazol-2-yl)thiopheneYield 276.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A portion of 2-iodo-4-(5-methylthiophen-2-yl)-1H-imidazole 3 (940 mg, 3.25 mmol), thiophene-2,5-diboronic acid (250 mg, 1.46 mmol), Na2CO3 (780 mg, 7.40 mmol) in H2O (5 mL) and DMF (40 mL) was degassed (N2 bubbling). Pd(PPh3)4 (85 mg) was added and the mixture was heated to reflux for 3 h. The mixture was allowed to cool to room temperature and concentrated. The mixture was diluted with EtOAc and H2O and the organic phase was separated. The aqueous phase was re-extracted (EtOAc) and the combined organics were washed (saturated aqueous NaCl), dried (MgSO4), filtered and concentrated to give a residue. The residue was purified by flash chromatography (EtOAc/hexanes 35:65 then 50:50 then 75:25) to give 2,5-bis(4-(5-methylthiophen-2-yl)-1H-imidazol-2-yl)thiophene 4 (1.65 g, 27%) as a pale brown solid. 1H NMR [(CD3)2SO, 400 MHz] δ2.44 (s, 6H), 6.75 (s, 2H), 7.11 (d, J=3.0 Hz, 2H), 7.51 (br s, 4H), 12.65-12.85 (br s, 2H); HRMS (EI) m/z 408.0539 C20H16N4S3 [M]+. requires 408.0532.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 3 h
  3. concentrationconcentrated
  4. additionThe mixture was diluted with EtOAc and H2O
  5. customthe organic phase was separated
  6. extractionThe aqueous phase was re-extracted (EtOAc)
  7. washthe combined organics were washed (saturated aqueous NaCl)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a residue
  12. customThe residue was purified by flash chromatography (EtOAc/hexanes 35:65

Sources & evidence

ORD record
ord-861bf55ccd4e474293ae8dcdffea3c7c
Source dataset
uspto-grants-2015_01
Patent number
US08937303B2

Reaction notes

Loading…