7-Chlorothieno[3,2-b]pyridine → HCID 58790172, compound

HRID 418725Notes

Reaction equation

HRID 418725 reaction equation
[Cl:1][C:2]1[C:7]2[S:8][CH:9]=[CH:10][C:6]=2[N:5]=[CH:4][CH:3]=1.C([Li])CCC.I[C:17]1[N:18]=[CH:19][N:20]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:21]=1>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:3]=[CH:4][N:5]=[C:6]2[CH:10]=[C:9]([C:17]3[N:18]=[CH:19][N:20]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:21]=3)[S:8][C:7]=12

Participants

7

Reactant 3

HCID 112752517-Chlorothieno[3,2-b]pyridineHCID 58790086HCID 58790086, compoundHCID 178418339Butyllithium

Product 1

HCID 58790172HCID 58790172, compoundYield 44.2%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 7-chlorothienopyridine (2.23 g, 13.1 mmol) in dry THF (50 mL) at −78° C. under N2 was added n-butyllithium (2.5 M in hexanes, 5.6 mL, 14 mmol), dropwise, with stirring. The resulting suspension was stirred for 30 min at −78° C., then ZnCl2 (0.5M in THF, 30 mL, 15 mmol) was added and the mixture was allowed to warm to 0° C. Imidazole 372 (3.20 g, 11.4 mmol) and tetrakis(triphenylphosphine)palladium (0.40 g, 0.35 mmol) in THF (50 mL) were then added to the aryllithium suspension, and the mixture was heated under reflux for 2 h, then cooled and concentrated. The residue was partitioned between ethyl acetate and water. The organic phase was collected, filtered, dried (anhydrous MgSO4), filtered again and concentrated. The resulting solid was triturated (1:1 ethyl acetate/hexanes) to afford 373 (1.62 g, 44% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.55 (d, J=5.1, 1H); 7.91 (d, J=1.2, 1H); 7.78 (d, J=1.2, 1H); 7.77 (s, 1H); 7.45 (d, J=5.2, 1H); 5.05 (s, 2H); 4.17 (q, J=7.2, 2H); 1.23 (t, J=7.0, 3H). LRMS (M+H): 322.0

Workup

  1. stirringThe resulting suspension was stirred for 30 min at −78° C.
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for 2 h
  4. temperaturecooled
  5. concentrationconcentrated
  6. customThe residue was partitioned between ethyl acetate and water
  7. customThe organic phase was collected
  8. filtrationfiltered
  9. dry with materialdried (anhydrous MgSO4)
  10. filtrationfiltered again
  11. concentrationconcentrated
  12. customThe resulting solid was triturated (1:1 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-c20da9d0f3b246259617d0ec64ab1fc2
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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