7-Chlorothieno[3,2-b]pyridine → HCID 67442617, compound

HRID 1400879Notes

Reaction equation

HRID 1400879 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.I[C:17]1[N:18]=[CH:19][N:20]([CH2:22][CH2:23][N:24]([CH2:32][CH2:33][O:34][CH3:35])[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH:21]=1>C1COCC1.[Cl-].[Cl-].[Zn+2]>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:17]3[N:18]=[CH:19][N:20]([CH2:22][CH2:23][N:24]([CH2:32][CH2:33][O:34][CH3:35])[C:25](=[O:31])[O:26][C:27]([CH3:29])([CH3:30])[CH3:28])[CH:21]=3)[S:10][C:3]=12

Participants

6

Reactant 3

HCID 112752517-Chlorothieno[3,2-b]pyridineHCID 67444137HCID 67444137, compoundHCID 178418339Butyllithium

Product 1

HCID 67442617HCID 67442617, compoundYield 99.3%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 7-chlorothieno[3,2-b]pyridine (1.39 g, 8.20 mmol) in THF (30 mL) at −15° C. was added n-BuLi (3.28 mL, 8.20 mmol). After 30 min, ZnCl2 (1.12 g, 8.20 mmol) was added at −15° C. and the reaction mixture was allowed to warm to RT over 45 min. A solution of palladium tetrakistriphenylphosphine (0.126 g, 0.11 mmol) and iodide 249 (2.16 g, 5.47 mmol) in THF (10 mL) was added and the mixture was heated to reflux for 45 min then concentrated. The reaction mixture was diluted with water and ammonium hydroxide and 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; MeOH/DCM: 0/100 to 10/90 over 20 CV), to afford the title compound 250 (2.37 g, 5.43 mmol, 99% yield) as light brown solid. MS (m/z): 437.45 (M+H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 45 min
  3. concentrationthen concentrated
  4. additionThe reaction mixture was diluted with water and ammonium hydroxide
  5. extractionextracted with DCM
  6. washThe extract was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by Biotage (SNAP 340 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV)

Sources & evidence

ORD record
ord-475596829a7242feb73faee48204c481
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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