Hydrochloric Acid → 2-(4-Chloro-phenyl)-6-[6-((s)-3-dimethylamino-pyrrolidin-1-yl)-pyridin-3-yl]-6h-thieno[2,3-c]pyridin-7-one, hydrochloride

HRID 423419Notes

Reaction equation

HRID 423419 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:17][C:11]3[C:12](=[O:16])[NH:13][CH:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.Br[C:19]1[CH:20]=[CH:21][C:22]([N:25]2[CH2:29][CH2:28][C@H:27]([N:30]([CH3:32])[CH3:31])[CH2:26]2)=[N:23][CH:24]=1.C([O-])([O-])=O.[Cs+].[Cs+].CNCCNC.Cl>O1CCOCC1.CCOC(C)=O.C(Cl)Cl.CCO.[Cu]I>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:17][C:11]3[C:12](=[O:16])[N:13]([C:19]4[CH:24]=[N:23][C:22]([N:25]5[CH2:29][CH2:28][C@H:27]([N:30]([CH3:32])[CH3:31])[CH2:26]5)=[CH:21][CH:20]=4)[CH:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:6][CH:7]=1

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 576495192-(4-Chlorophenyl)-6H,7H-thieno[2,3-c]pyridin-7-oneHCID 60052291(3S)-1-(5-bromo-2-pyridinyl)-N,N-dimethyl-3-pyrrolidinamine

Product 1

HCID 247593522-(4-Chloro-phenyl)-6-[6-((s)-3-dimethylamino-pyrrolidin-1-yl)-pyridin-3-yl]-6h-thieno[2,3-c]pyridin-7-one, hydrochlorideYield 116.4%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Combine 2-(4-chloro-phenyl)-6H-thieno[2,3-c]pyridin-7-one (0.2575 g, 0.98 mmol), [(S)-1-(5-bromo-pyridin-2-yl)-pyrrolidin-3-yl]-dimethyl-amine (Goodfellow, V.; et. al. US 2005012853) (0.3184 g, 1.18 mmol), and Cs2CO3 (0.64 g, 1.96 mmol) in dioxane (25 mL). Degass the suspension by purging with nitrogen for 5 min. Add CuI (37 mg, 0.20 mmol) and N,N′-dimethylethylenediamine (35 mg). Stir the reaction mixture at 100° C. overnight. Cool to RT and dilute with EtOAc (100 mL). Wash with a solution of H2O/NH3.H2O (2×30 mL/2 mL). Dry the organic layer over Na2SO4, filter and concentrate. Purify the crude material by chromatography by eluting with 2% NH3.H2O, 50% CH3OH/EtOAc to provide 0.258 g. Dissolve the material in CH2Cl2 (5 mL) and treat with 1.0 M HCl in EtOH (0.57 mL) to provide 0.278 g (58%) of the title compound. LC-MS/ES m/z (35Cl) 451.2 (M+H)+.

Workup

  1. customDegass the suspension
  2. customby purging with nitrogen for 5 min
  3. temperatureCool to RT
  4. washWash with a solution of H2O/NH3.H2O (2×30 mL/2 mL)
  5. dry with materialDry the organic layer over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate
  8. customPurify the crude material by chromatography
  9. washby eluting with 2% NH3.H2O, 50% CH3OH/EtOAc
  10. customto provide 0.258 g

Sources & evidence

ORD record
ord-782bb23ef4914558bc98d08c8e711aac
Source dataset
uspto-grants-2012_01
Patent number
US08101764B2

Reaction notes

Loading…