7-Chlorothieno[3,2-b]pyridine → HCID 67441824, compound

HRID 1400902Notes

Reaction equation

HRID 1400902 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.Br[C:17]1[N:22]=[CH:21][C:20]([CH2:23][CH2:24][N:25]([CH2:33][CH2:34][O:35][CH3:36])[C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:19][CH:18]=1>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:17]3[N:22]=[CH:21][C:20]([CH2:23][CH2:24][N:25]([CH2:33][CH2:34][O:35][CH3:36])[C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:29])[CH3:30])=[CH:19][CH:18]=3)[S:10][C:3]=12

Participants

5

Reactant 3

HCID 112752517-Chlorothieno[3,2-b]pyridineHCID 86658598HCID 86658598, compoundHCID 178418339Butyllithium

Product 1

HCID 67441824HCID 67441824, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 7-chlorothieno[3,2-b]pyridine (4.26 g, 25.09 mmol) in THF (64 mL) at −15° C. was added n-BuLi (10.77 mL, 25.09 mmol). After 30 min, ZincCl2 (3.42 g, 25.09 mmol) was added at −15° C. and the reaction mixture was allowed to warm to RT over 45 min. A solution of palladium tetrakistriphenylphosphine (0.387 g, 0.335 mmol) and bromide 285 (6.01 g, 16.73 mmol) in THF (20 mL) was added and the mixture was heated to reflux for 1 h and concentrated. The reaction was quenched by addition of water and ammonium hydroxide and the mixture was extracted with DCM. The extract was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by Biotage (SNAP 340 g cartridge; AcOEt/Hex:50/50 to 100/0 over 20 CV), to afford title compound 286 (3.74 g, 8.35 mmol, 50% yield) as yellow oil. MS (m/z): 448.48 (M+H).

Workup

  1. additionZincCl2 (3.42 g, 25.09 mmol) was added at −15° C.
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 1 h
  4. concentrationconcentrated
  5. customThe reaction was quenched by addition of water and ammonium hydroxide
  6. extractionthe mixture was extracted with DCM
  7. washThe extract was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by Biotage (SNAP 340 g cartridge; AcOEt/Hex:50/50 to 100/0 over 20 CV)

Sources & evidence

ORD record
ord-483e8d7c5e404728812ece5eaade5932
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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