N,N'-Dimethylethylenediamine → 3-{4-[2-(4-chloro-phenyl)-7-oxo-7H-thieno[2,3-c]pyridin-6-yl]-phenylcarbamoyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2384944Notes

Reaction equation

HRID 2384944 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13](=[O:15])[NH2:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH:28]=[CH:27][C:26]3[CH:29]=[C:30]([C:32]4[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=4)[S:31][C:25]=3[C:24]2=[O:39])=[CH:19][CH:18]=1.C([O-])([O-])=O.[Cs+].[Cs+].CNCCNC>C(Cl)Cl.[Cu]I.O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13](=[O:15])[NH:14][C:17]2[CH:18]=[CH:19][C:20]([N:23]3[CH:28]=[CH:27][C:26]4[CH:29]=[C:30]([C:32]5[CH:33]=[CH:34][C:35]([Cl:38])=[CH:36][CH:37]=5)[S:31][C:25]=4[C:24]3=[O:39])=[CH:21][CH:22]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 4571096Tert-butyl 3-carbamoylpyrrolidine-1-carboxylateHCID 689531476-(4-Bromo-phenyl)-2-(4-chloro-phenyl)-6H-thieno[2,3-c]pyridin-7-one

Product 1

HCID 689499533-{4-[2-(4-chloro-phenyl)-7-oxo-7H-thieno[2,3-c]pyridin-6-yl]-phenylcarbamoyl}-pyrrolidine-1-carboxylic acid tert-butyl esterYield 44.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

Combine 3-carbamoyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.21 g, 0.96 mmol), 6-(4-bromo-phenyl)-2-(4-chloro-phenyl)-6H-thieno[2,3-c]pyridin-7-one (0.2 g, 0.48 mmol), Cs2CO3 (0.31 g, 0.96 mmol), 1,4-dioxane (5 mL), and CuI (0.037 g, 0.19 mmol). Purge the mixture with nitrogen for 10 min and then add sym-dimethylethylene diamine (0.034 g, 0.38 mmol). 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. Dry the organic layer over Na2SO4, filter, and concentrate. Filter the crude with Et2O and water to give 0.117 g (43%) of the title compound. LC-ES/MS m/z (35Cl) 494.0 [M−tert Bu+H]+.

Workup

  1. customPurge the mixture with nitrogen for 10 min
  2. temperatureCool the mixture to RT
  3. washwash twice with a solution of 5% NH4OH/H2O
  4. dry with materialDry the organic layer over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate
  7. filtrationFilter the crude with Et2O and water

Sources & evidence

ORD record
ord-eafeb7b904644c9a89391d63f45a4647
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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