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

HRID 2384882Notes

Reaction equation

HRID 2384882 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][C:11]3[CH:14]=[C:15]([C:17]4[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=4)[S:16][C:10]=3[C:9]2=[O:25])=[CH:4][C:3]=1[O:26][CH3:27].Cl.[Cl:29][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.[H-].[Na+].Cl.CCOC(C)=O>CN(C=O)C.CO>[ClH:29].[CH3:27][O:26][C:3]1[CH:4]=[C:5]([N:8]2[CH2:13][CH2:12][C:11]3[CH:14]=[C:15]([C:17]4[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=4)[S:16][C:10]=3[C:9]2=[O:25])[CH:6]=[CH:7][C:2]=1[O:1][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 689509596-(4-Hydroxy-3-methoxy-phenyl)-2-(4-methoxy-phenyl)-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-one

Product 1

HCID 248030836-[3-Methoxy-4-(2-morpholin-4-yl-ethoxy)-phenyl]-2-(4-methoxy-phenyl)-5,6-dihydro-4h-thieno[2,3-c]pyridin-7-one, hydrochlorideYield 20%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Treat 6-(4-hydroxy-3-methoxy-phenyl)-2-(4-methoxy-phenyl)-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-one (0.12 g, 0.31 mmol) in DMF (5 mL) with 4-(2-chloro-ethyl)-morpholine hydrochloride salt (59 mg, 0.31 mmol) and 60% NaH (38 mg, 0.94 mmol). Stir the reaction at 85° C. overnight. Quench with water (5 mL) and dilute with EtOAc (150 mL). Separate the phases and wash the organic phase with water (3×50 mL), dry over Na2SO4, filter, and concentrate. Purify the crude material by chromatography, eluting with 1% NH3—H2O, 10% CH3OH and 90% EtOAc to give 31 mg. Dissolve the material in CH3OH (2 mL), and treat with 1.0 M HCl in EtOAc (65 μL, 0.065 mmol), with stirring at RT for 5 min. Remove the solvent in vacuo to give 33 mg (20%) of the title compound. LC-MS/ES m/z 495.0 [M+H]+.

Workup

  1. customthe reaction at 85° C. overnight
  2. customQuench with water (5 mL)
  3. additiondilute with EtOAc (150 mL)
  4. customSeparate the phases
  5. washwash the organic phase with water (3×50 mL)
  6. dry with materialdry over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate
  9. customPurify the crude material by chromatography
  10. washeluting with 1% NH3—H2O, 10% CH3OH and 90% EtOAc
  11. customto give 31 mg
  12. stirringwith stirring at RT for 5 min
  13. customRemove the solvent in vacuo

Sources & evidence

ORD record
ord-d3a22ab9170944b99f8694dedd1402d2
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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