Hydrochloric Acid → 2-(4-Methoxy-phenyl)-6-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6-dihydro-4h-thieno[2,3-c]pyridin-7-one, hydrochloride

HRID 2384881Notes

Reaction equation

HRID 2384881 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:18][C:12]3[C:13](=[O:17])[NH:14][CH2:15][CH2:16][C:11]=3[CH:10]=2)=[CH:5][CH:4]=1.Br[C:20]1[CH:33]=[CH:32][C:23]([O:24][CH2:25][CH2:26][N:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)=[C:22]([O:34][CH3:35])[CH:21]=1.CNCCNC.C([O-])([O-])=O.[K+].[K+].[ClH:48].CCO>C1(C)C=CC=CC=1.CCOC(C)=O.CO.[Cu]I>[ClH:48].[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:18][C:12]3[C:13](=[O:17])[N:14]([C:20]4[CH:33]=[CH:32][C:23]([O:24][CH2:25][CH2:26][N:27]5[CH2:28][CH2:29][CH2:30][CH2:31]5)=[C:22]([O:34][CH3:35])[CH:21]=4)[CH2:15][CH2:16][C:11]=3[CH:10]=2)=[CH:5][CH:4]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 702EthanolHCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 229943381-[2-(4-Bromo-2-methoxyphenoxy)ethyl]pyrrolidineHCID 576495112-(4-Methoxy-phenyl)-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-one

Product 1

HCID 248030812-(4-Methoxy-phenyl)-6-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6-dihydro-4h-thieno[2,3-c]pyridin-7-one, hydrochlorideYield 100%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 887MethanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combine 2-(4-methoxy-phenyl)-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-one (0.234 g, 0.90 mmol), 1-[2-(4-bromo-2-methoxy-phenoxy)-ethyl]-pyrrolidine (Bastian, J. A., et al WO 9725033 A1) (0.271 g, 0.90 mmol), N,N′-dimethyl-ethane-1,2-diamine (16 mg, 0.18 mmol), K2CO3 (0.249 g, 1.81 mmol), and CuI (17 mmol, 0.09 mmol) in toluene (10 mL) and stir at 110° C. for 48 h. Dilute with EtOAc (100 mL) and wash with water (50 mL), containing NH3—H2O (5 mL) three times. Dry over Na2SO4, filter and purify the material by chromatography, eluting with 7% 2 M NH3 in CH3OH, and 93% CH2Cl2 to give 0.125 g. Dissolve the material in CH3OH (5 mL) and treat with 1.0 M HCl in EtOH (270 μL, 0.27 mmol). Stir at RT for 5 min and concentrate to give the title compound (0.133 g, 0.26 mmol, 100%). LC-MS/ES m/z 479.3 [M+H]+.

Workup

  1. washwash with water (50 mL)
  2. additioncontaining NH3—H2O (5 mL) three times
  3. dry with materialDry over Na2SO4
  4. filtrationfilter
  5. custompurify the material by chromatography
  6. washeluting with 7% 2 M NH3 in CH3OH, and 93% CH2Cl2
  7. customto give 0.125 g
  8. concentrationconcentrate

Sources & evidence

ORD record
ord-7b7873e97f424edf85cd0566cf867cf3
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

Loading…