Cesium carbonate → Toluene-4-sulfonic acid 2-methoxy-4-[2-(4-methoxy-phenyl)-7-oxo-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-phenyl ester

HRID 2384879Notes

Reaction equation

HRID 2384879 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:25]=[CH:24][C:23]([O:26][S:27]([C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)(=[O:29])=[O:28])=[C:22]([O:37][CH3:38])[CH:21]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[CH3:38][O:37][C:22]1[CH:21]=[C:20]([N:14]2[CH2:15][CH2:16][C:11]3[CH:10]=[C:9]([C:6]4[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[S:18][C:12]=3[C:13]2=[O:17])[CH:25]=[CH:24][C:23]=1[O:26][S:27]([C:30]1[CH:31]=[CH:32][C:33]([CH3:36])=[CH:34][CH:35]=1)(=[O:29])=[O:28]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 576495112-(4-Methoxy-phenyl)-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-oneHCID 866292054-Bromo-2-methoxyphenyl 4-methylbenzene-1-sulfonate

Product 1

HCID 57649518Toluene-4-sulfonic acid 2-methoxy-4-[2-(4-methoxy-phenyl)-7-oxo-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-phenyl esterYield 86%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Combine 2-(4-methoxy-phenyl)-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-one (0.245 g, 0.943 mmol), toluene-4-sulfonic acid 4-bromo-2-methoxy-phenyl ester (0.404 g, 1.13 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos) (27.3 mg, 0.05 mmol), and Cs2CO3 (0.461 g, 1.41 mmol) in dioxane (25 mL). Purge the reaction vessel with nitrogen for 5 min, and then add Pd2(dba)3 (8.6 mg, 0.09 mmol). Reflux the reaction mixture and stir 16 h. Dilute with EtOAc (100 mL), wash with water (2×30 mL), dry with Na2SO4, filter and concentrate. Purify the crude material by chromatography, eluting with 30-50% EtOAc/hexanes to give 0.432 g (86%) of the title compound. LC-MS/ES m/z 536.0 [M+H]+.

Workup

  1. customPurge the reaction vessel with nitrogen for 5 min
  2. temperatureReflux the reaction mixture
  3. washwash with water (2×30 mL)
  4. dry with materialdry with Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the crude material by chromatography
  8. washeluting with 30-50% EtOAc/hexanes

Sources & evidence

ORD record
ord-f0e50bf4497d4795b82413b4739b8bf4
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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