7-Chlorothieno[3,2-b]pyridine → HCID 59424433, compound

HRID 500784Notes

Reaction equation

HRID 500784 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[CH:9][S:10][C:3]=12.[Li]CCCC.[CH2:16]([N:18]1[C:22]([CH3:23])=[C:21](I)[N:20]=[CH:19]1)[CH3:17]>C1COCC1.[Cl-].[Cl-].[Zn+2].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>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:21]3[N:20]=[CH:19][N:18]([CH2:16][CH3:17])[C:22]=3[CH3:23])[S:10][C:3]=12

Participants

7

Reactant 3

HCID 112752517-Chlorothieno[3,2-b]pyridineHCID 59424668HCID 59424668, compoundHCID 178418339Butyllithium

Product 1

HCID 59424433HCID 59424433, compoundYield 117.2%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2 (1.14 g, 6.76 mmol) in THF (60 ml) was added, at −78° C., n-BuLi (3.38 ml, 2.5 M soln in hexanes) and the reaction mixture was stirred at the same temperature for 10 min. A solution of ZnCl2 (16.9 ml, 2.5 ml, 0.5M in THF) was added and the reaction mixture was warmed to room temperature. Then a solution of 1-ethyl-4-iodo-5-methyl-1H-imidazole (800 mg, 3.38 mmol) (Pyne, S. G and Cliff, M. D. Synthesis 1994, 681) and Pd(PPh3)4 (390 mg, 0.34 mmol) in THF (15 ml) were added and the reaction mixture was refluxed for 3 hrs, cooled to room temperature, quenched with conc. ammonium hydroxide solution and made neutral with concentrated aqueous HCl. The neutral solution was extracted with EtOAc, the extract was collected, dried over anhydrous sodium sulfate, and filtered. The filtrate was evaporated and the residue was purified by column chromatography (eluent MeOH:EtOAc, 1:9) to afford the title compound 87 (1.1 g, 100% yield) as a brown oil. MS (m/z) 278.0/280.0 (M+H).

Workup

  1. temperaturethe reaction mixture was refluxed for 3 hrs
  2. temperaturecooled to room temperature
  3. customquenched with conc. ammonium hydroxide solution
  4. extractionThe neutral solution was extracted with EtOAc
  5. customthe extract was collected
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customThe filtrate was evaporated
  9. customthe residue was purified by column chromatography (eluent MeOH:EtOAc, 1:9)

Sources & evidence

ORD record
ord-1b6458bdb8de48c3bda48b96988aa99b
Source dataset
uspto-grants-2010_08
Patent number
US07772247B2

Reaction notes

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