Diethyl Ether → tert-butyl 4-(2-(4-(7-chlorothieno[3,2-b]pyridin-2-yl)-1H-imidazol-1-yl)ethyl)piperazine-1-carboxylate

HRID 1400917Notes

Reaction equation

HRID 1400917 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.CCOCC.I[C:22]1[N:23]=[CH:24][N:25]([CH2:27][CH2:28][N:29]2[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]2)[CH:26]=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:22]3[N:23]=[CH:24][N:25]([CH2:27][CH2:28][N:29]4[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]4)[CH:26]=3)[S:10][C:3]=12

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 112752517-Chlorothieno[3,2-b]pyridineHCID 67442735tert-butyl 4-(2-(4-iodo-1H-imidazol-1-yl)ethyl)piperazine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 67442621tert-butyl 4-(2-(4-(7-chlorothieno[3,2-b]pyridin-2-yl)-1H-imidazol-1-yl)ethyl)piperazine-1-carboxylateYield 72.2%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 7-chlorothieno[3,2-b]pyridine (2.95 g, 17.39 mmol) in THF (60 ml) at −15° C. was added n-BuLi (2.5M, 6.96 ml, 17.39 mmol). After 30 min, a solution of ZnCl2 in Et2O (1M, 17.39 mL, 17.39 mmol) was added at −15° C. and the reaction mixture was warmed to RT over 45 min. A solution of palladium tetrakistriphenylphosphine (0.268 g, 0.232 mmol) and 304 (4.71 g, 11.59 mmol) in THF (18 ml) was added and the mixture was heated to reflux for 1 h then concentrated. The residue was diluted with water and ammonium hydroxide and extracted with DCM. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was triturated with a mixture of MTBE/Hexane, to afford the title compound 305 (3.75 g, 8.37 mmol, 72% yield) as a beige solid. MS (m/z): 448.46 (M+H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 1 h
  3. concentrationthen concentrated
  4. additionThe residue was diluted with water and ammonium hydroxide
  5. extractionextracted with DCM
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was triturated with a mixture of MTBE/Hexane

Sources & evidence

ORD record
ord-fbf6f061aaae465f8297cacd036703a1
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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