Hydrochloric Acid → 2-(4-Chloro-phenyl)-6-[3-methoxy-4-(3-methyl-3h-imidazol-4-ylmethoxy)-phenyl]-6h-thieno[2,3-c]pyridin-7-one, hydrochloride

HRID 2384920Notes

Reaction equation

HRID 2384920 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:26][CH:11]3[C:12](=[O:25])[N:13]([C:16]4[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([O:23][CH3:24])[CH:17]=4)[CH:14]=[CH:15][CH:10]3[CH:9]=2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Cl.Cl[CH2:35][C:36]1[N:40]([CH3:41])[CH:39]=[N:38][CH:37]=1.Cl>CN1C(=O)CCC1.C(Cl)(Cl)Cl.CO.CCO.CCOC(C)=O>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:26][C:11]3[C:12](=[O:25])[N:13]([C:16]4[CH:21]=[CH:20][C:19]([O:22][CH2:35][C:36]5[N:40]([CH3:41])[CH:39]=[N:38][CH:37]=5)=[C:18]([O:23][CH3:24])[CH:17]=4)[CH:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 142396965-(chloromethyl)-1-methyl-1H-imidazole hydrochlorideHCID 689502812-(4-Chloro-phenyl)-6-(4-hydroxy-3-methoxy-phenyl)-3a,7a-dihydro-6H-thieno[2,3-c]pyridin-7-one

Product 1

HCID 248035852-(4-Chloro-phenyl)-6-[3-methoxy-4-(3-methyl-3h-imidazol-4-ylmethoxy)-phenyl]-6h-thieno[2,3-c]pyridin-7-one, hydrochlorideYield 56.9%

Reagents, catalysts & solvents 5

HCID 702EthanolSolventHCID 887MethanolSolventHCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

Dissolve 2-(4-chloro-phenyl)-6-(4-hydroxy-3-methoxy-phenyl)-3a,7a-dihydro-6H-thieno[2,3-c]pyridin-7-one (0.271 g, 0.71 mmol) in NMP (10 mL) and treat with K2CO3 (0.39 g, 2.83 mmol), and 5-chloromethyl-1-methyl-1H-imidazole hydrochloride salt (123 mg, 0.74 mmol). Stir the mixture at 80° C. overnight. Dilute the reaction with EtOAc (100 mL), wash with water (3×25 mL), dry over Na2SO4, filter and concentrate. Purify the crude material by chromatography, eluting with 1% NH3—H2O, 30% CH3OH/EtOAc to give 0.105 g. Dissolve the material in CHCl3 (5 mL) and CH3OH (2 mL). Add 1.0 M HCl in EtOH (213 μL) stir. Concentrate and dry in vacuo to give 0.104 g (28%) of the title compound. LC-MS/ES m/z (37Cl) 479.0 [M+]. 1H NMR (DMSO-d6) δ 3.79 (s, 3H), 3.92 (s, 3H), 5.30 (s, 2H), 6.83 (d, J=7.2 Hz, 1H), 7.03 (dd, J=8.3, 2.1 Hz, 1H), 7.17 (d, J=2.1 Hz, 1H), 7.30 (d, J=8.7 Hz, 1H), 7.5 (d, J=7.2 Hz, 1H), 7.58 (d, J=8.5 Hz, 2H), 7.83 (d, J=8.5 Hz, 2H), 7.88 (s, 3H), 9.07 (bs, 1H).

Workup

  1. additionDilute
  2. washwash with water (3×25 mL)
  3. dry with materialdry over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify the crude material by chromatography
  7. washeluting with 1% NH3—H2O, 30% CH3OH/EtOAc
  8. customto give 0.105 g
  9. stirringstir
  10. concentrationConcentrate
  11. customdry in vacuo

Sources & evidence

ORD record
ord-be4dcef7b49b4ef9a32195c194c2ab11
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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