N,N'-Dimethylethylenediamine → 2-(4-Chloro-phenyl)-6-[4-(1-methyl-pyrrolidine-3-carbonyl)-phenyl]-6h-thieno[2,3-c]pyridin-7-one, hydrochloride

HRID 2384943Notes

Reaction equation

HRID 2384943 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:24]=[CH:23][C:22]([C:25]([CH:27]2[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28]2)=[O:26])=[CH:21][CH:20]=1.C([O-])([O-])=O.[Cs+].[Cs+].CNCCNC.Cl.CCOCC>C(Cl)Cl.[Cu]I.O1CCOCC1>[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]=[CH:23][C:22]([C:25]([CH:27]5[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28]5)=[O:26])=[CH:21][CH:20]=4)[CH:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 10953452Ether hydrochlorideHCID 576495192-(4-Chlorophenyl)-6H,7H-thieno[2,3-c]pyridin-7-oneHCID 68951075HCID 68951075, compound

Product 1

HCID 248037462-(4-Chloro-phenyl)-6-[4-(1-methyl-pyrrolidine-3-carbonyl)-phenyl]-6h-thieno[2,3-c]pyridin-7-one, hydrochlorideYield 151.8%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Combine 2-(4-chloro-phenyl)-6H-thieno[2,3-c]pyridin-7-one (0.15 g, 0.57 mmol), (4-bromo-phenyl)-(1-methyl-pyrrolidin-3-yl)-methanone (0.16 g, 0.60 mmol), Cs2CO3 (0.37 g, 1.15 mmol), 1,4-dioxane (6 mL), and CuI (0.044 g, 0.23 mmol). Purge the mixture with nitrogen for 10 min. Add sym-dimethylethylene diamine (0.040 g, 0.46 mmol). Heat the mixture at 100° C. overnight. Cool the mixture to RT, dilute with CH2Cl2 (200 mL), and wash with a solution of 5% NH4OH/H2O (2×30 mL). Dry the organic layer over Na2SO4, filter, and concentrate. Filter the crude with H2O (200 mL) and Et2O (100 mL). Prepare the HCl salt by dissolving the solid in CH2Cl2 and adding 1 eq 1M HCl/ether. Allow the solution to stir for 15 min and concentrate to give 0.21 g (77%) of the title compound. LC-MS/ES m/z (35Cl) 449.0 [M+H]+.

Workup

  1. customPurge the mixture with nitrogen for 10 min
  2. temperatureCool the mixture to RT
  3. washwash with a solution of 5% NH4OH/H2O (2×30 mL)
  4. dry with materialDry the organic layer over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate
  7. filtrationFilter the crude with H2O (200 mL) and Et2O (100 mL)
  8. customPrepare the HCl salt
  9. concentrationconcentrate

Sources & evidence

ORD record
ord-3ec9ae2f2d854c2fb27b702b4996fa66
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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