Cesium carbonate → 7-(6-Chloropyridin-3-yloxy)-2-iodothieno[3,2-b]pyridine

HRID 1676325Notes

Reaction equation

HRID 1676325 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([I:11])[S:10][C:3]=12.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:18][C:19]1[N:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=1>CN(C=O)C>[Cl:18][C:19]1[N:24]=[CH:23][C:22]([O:25][C:2]2[CH:7]=[CH:6][N:5]=[C:4]3[CH:8]=[C:9]([I:11])[S:10][C:3]=23)=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 8198212-Chloro-5-hydroxypyridineHCID 177504007-Chloro-2-iodothieno(3,2-b)pyridine

Product 1

HCID 866146527-(6-Chloropyridin-3-yloxy)-2-iodothieno[3,2-b]pyridineYield 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Related methodology was described in WO 2005/121125. A stirred mixture of 7-chloro-2-iodothieno[3,2-b]pyridine (1.48 g, 5.00 mmol, prepared according to Ragan, J. A. Org. Proc. Res. 2003, 7, 676), cesium carbonate (2.44 g, 7.50 mmol), and DMF (50 mL) was heated to 135° C. under nitrogen with an attached reflux condenser. Next a solution of 6-chloropyridin-3-ol (0.972 g, 7.50 mmol) in DMF (20 mL) was added dropwise by syringe (2 mL approx every 5 min over a period of 50 minutes). The reaction was heated for 4 hours more after addition was complete. The reaction was left stirring at room temperature for 18 hours for convenience. The dark mixture was partitioned between EtOAc (100 mL) and water (100 mL). The phases were separated, and the aqueous phase was re-extracted with EtOAc (50 mL). The combined organic phases were washed with water (3×200 mL), brine (200 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The crude was purified by Biotage Flash 40M, eluting with 20% EtOAc/hexanes (1 L) followed by 1:1 EtOAc/hexanes (1 L). The product was obtained as a beige solid (628 mg, 32%). 1H NMR (400 MHz, CDCl3) δ 8.49 (d, J=6 Hz, 1H), 8.33 (d, J=2 Hz, 1H), 7.80 (s, 1H), 7.48 (m, 1H), 7.43 (d, J=9 Hz, 1H), 6.54 (d, J=6 Hz, 1H).

Workup

  1. customprepared
  2. temperaturean attached reflux condenser
  3. temperatureThe reaction was heated for 4 hours
  4. additionmore after addition
  5. waitThe reaction was left
  6. customThe dark mixture was partitioned between EtOAc (100 mL) and water (100 mL)
  7. customThe phases were separated
  8. extractionthe aqueous phase was re-extracted with EtOAc (50 mL)
  9. washThe combined organic phases were washed with water (3×200 mL), brine (200 mL)
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe crude was purified by Biotage Flash 40M
  14. washeluting with 20% EtOAc/hexanes (1 L)

Sources & evidence

ORD record
ord-1e00b4292e8f431c9d84d529cd8b01df
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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