N,N'-Dimethylethylenediamine → HCID 24803251, compound

HRID 2384899Notes

Reaction equation

HRID 2384899 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]([NH:25][C:26](=[O:33])[CH2:27][N:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)=[C:21]([O:34][CH3:35])[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]([NH:25][C:26](=[O:33])[CH2:27][N:28]5[CH2:32][CH2:31][CH2:30][CH2:29]5)=[C:21]([O:34][CH3:35])[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 68948398HCID 68948398, compound

Product 1

HCID 24803251HCID 24803251, compoundYield 106.9%

Reagents, catalysts & solvents 3

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

Procedure

Combine 2-(4-chloro-phenyl)-6H-thieno[2,3-c]pyridin-7-one (1.8 g, 6.88 mmol), N-(4-bromo-2-methoxy-phenyl)-2-pyrrolidin-1-yl-acetamide (2.58 g, 8.25 mmol), Cs2CO3 (4.48 g, 13.8 mmol), 1,4-dioxane (69 mL), and CuI (0.520 g, 2.75 mmol). Purge the mixture with nitrogen for 10 min. Add sym-dimethylethylene diamine (0.49 g, 5.50 mmol) and heat the mixture at 100° C. overnight. Cool the mixture to RT, dilute with CH2Cl2, and wash twice with a solution of 5% NH4OH/H2O (2×). Dry the organic layer over Na2SO4, filter, and concentrate. Filter the crude with H2O and Et2O. Purify the crude material by chromatography using a gradient of 20-50% acetone in hexane. Prepare the HCl salt by dissolving the solid with CH2Cl2. Add 1 eq of 1 M HCl/ether, allow the solution to stir for 15 min, and concentrate to give 1.95 g (53%) of the title compound. LC-ES/MS m/z (35Cl) 494.0 [M+H]+.

Workup

  1. customPurge the mixture with nitrogen for 10 min
  2. washwash twice with a solution of 5% NH4OH/H2O (2×)
  3. dry with materialDry the organic layer over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate
  6. filtrationFilter the crude with H2O and Et2O
  7. customPurify the crude material by chromatography
  8. customPrepare the HCl salt
  9. concentrationconcentrate

Sources & evidence

ORD record
ord-674b0c068a744fc89b19d7e99e6d9a11
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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