Cesium carbonate → HCID 57625128, compound

HRID 888450Notes

Reaction equation

HRID 888450 reaction equation
Br[C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Br:9])[N:3]=1.[S:10]1[C:14]([C:15]([NH2:17])=[O:16])=[CH:13][C:12]2[CH2:18][CH2:19][CH2:20][CH2:21][C:11]1=2.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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].O1CCOCC1>[Br:9][C:4]1[N:3]=[C:2]([NH:17][C:15]([C:14]2[S:10][C:11]3[CH2:21][CH2:20][CH2:19][CH2:18][C:12]=3[CH:13]=2)=[O:16])[C:7]([F:8])=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 122315074,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamideHCID 529112372,6-Dibromo-3-fluoropyridine

Product 1

HCID 57625128HCID 57625128, compoundYield 37.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A 1-L three-neck round-bottomed flask equipped with a mechanical stirrer, reflux condenser and nitrogen inlet was charged with 1,4-dioxane (56 mL), 37 (3.00 g, 11.7 mmol),4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide (1.29 g, 7.12 mmol) and cesium carbonate (5.09 g, 15.6 mmol). After bubbling nitrogen through the resulting solution for 30 min, Xantphos (350 mg, 0.605 mmol) and tris(dibenzylideneacetone)-dipalladium(0) (326 mg, 0.365 mmol) were added and the reaction mixture was heated at reflux for 2 h. After this time the reaction was cooled to room temperature and filtered through, a pad of Celite 521. The filter cake was washed with methylene chloride (50 mL). The filtrate was concentrated under reduced pressure and the resulting residue was purified by column chromatography using 500 cc of silica and eluting with 5% EtOAc/hexanes to afford a 37% yield of 38 (940 mg) a white solid: Rf=0.55 (20% ethyl acetate in hexanes); 1H NMR (500 MHz, CDCl3) 7.80 (bs, 1H), 7.38 (m, 1H), 7.37 (s, 1H), 7.32 (dd, 1H, J=3.0, 8.0 Hz), 2.81 (t, 2H, J=6.5 Hz), 2.64 (t, 2H, J=6.0 Hz), 1.85 (m, 4H); MS (ESI+) m/z 355.1 (M+H) and N-(6-bromo-5-fluoropyridin-2-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide in 34% yield as a white solid: Rf=0.85 (20% ethyl acetate in hexanes); 1H NMR (500 MHz, CDCl3) 8.29 (dd, 1H, J=3.5, 9.0 Hz), 8.24 (bs, 1H), 7.47 (dd, 1H, m), 7.33 (s; 1H), 2.81 (t, 2H, J=6.5 Hz), 2.64 (t, 2H, J=6.0 Hz), 1.85 (m, 4H); MS (ESI+) m/z 355.1 (M+H).

Workup

  1. customA 1-L three-neck round-bottomed flask equipped with a mechanical stirrer
  2. temperaturereflux condenser and nitrogen inlet
  3. customAfter bubbling nitrogen through the resulting solution for 30 min
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 2 h
  6. filtrationfiltered through, a pad of Celite 521
  7. washThe filter cake was washed with methylene chloride (50 mL)
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe resulting residue was purified by column chromatography
  10. washeluting with 5% EtOAc/hexanes

Sources & evidence

ORD record
ord-765ca30790be47a6b69b90829cd5a868
Source dataset
uspto-grants-2012_08
Patent number
US08247550B2

Reaction notes

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