Potassium Carbonate → 7-(2-Fluoro-4-nitrophenoxy)-2-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)thieno[3,2-b]pyridine

HRID 1711094Notes

Reaction equation

HRID 1711094 reaction equation
FC(F)(F)S(O[C:7]1[CH2:8][CH2:9][N:10]([CH3:13])[CH2:11][CH:12]=1)(=O)=O.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[K+].[K+].Br[C:41]1[S:49][C:48]2[C:43](=[N:44][CH:45]=[CH:46][C:47]=2[O:50][C:51]2[CH:56]=[CH:55][C:54]([N+:57]([O-:59])=[O:58])=[CH:53][C:52]=2[F:60])[CH:42]=1.[F-].[Cs+].C([O-])(O)=O.[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:60][C:52]1[CH:53]=[C:54]([N+:57]([O-:59])=[O:58])[CH:55]=[CH:56][C:51]=1[O:50][C:47]1[CH:46]=[CH:45][N:44]=[C:43]2[CH:42]=[C:41]([C:7]3[CH2:8][CH2:9][N:10]([CH3:13])[CH2:11][CH:12]=3)[S:49][C:48]=12

Participants

10

Reactant 6

HCID 11430Potassium CarbonateHCID 25953Cesium fluorideHCID 516892Sodium BicarbonateHCID 2733548Bis(pinacolato)diboraneHCID 113795771-Methyl-1,2,3,6-tetrahydropyridin-4-yl trifluoromethanesulfonateHCID 594245212-Bromo-7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridine

Product 1

HCID 594577227-(2-Fluoro-4-nitrophenoxy)-2-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)thieno[3,2-b]pyridineYield 39.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of the triflate 377 (450 mg, 1.84 mmol), bis(pinacolato)diboron (477 mg, 2.02 mmol) and K2CO3 (541 mg, 5.52 mmol) in DME (3.7 mg), Pd(PPh3)4 (106 mg, 0.092 mmol) was added in one portion and the system was heated to reflux for 2 h under N2. The reaction mixture was cooled and filtered. To the filtrate containing the intermediate 378 were added bromide 42 (435 mg, 1.84 mmol, scheme 8), CsF (838 mg, 5.52 mmol), NaHCO3 (463 mg, 5.52 mmol) and water (0.8 mL), and the mixture was heated to reflux for additional 2 h. It was then diluted with water and extracted with DCM; the organic solution was extracted with 1N HCl, the aqueous phase was basified to pH˜11 by addition of 2N aqueous NaOH, extracted with DCM; the extract was dried over anhydrous Na2SO4 and concentrated under reduced pressure affording 379 (279 mg, 39% yield) as a brown solid. LCMS:(M+H) 385.9.

Workup

  1. additionwas added in one portion
  2. temperaturethe system was heated
  3. temperatureto reflux for 2 h under N2
  4. temperatureThe reaction mixture was cooled
  5. filtrationfiltered
  6. additionTo the filtrate containing the intermediate 378
  7. temperaturethe mixture was heated
  8. temperatureto reflux for additional 2 h
  9. extractionextracted with DCM
  10. extractionthe organic solution was extracted with 1N HCl
  11. additionthe aqueous phase was basified to pH˜11 by addition of 2N aqueous NaOH
  12. extractionextracted with DCM
  13. dry with materialthe extract was dried over anhydrous Na2SO4
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bf4b271eacd14d76b74d70784b014bc6
Source dataset
uspto-grants-2010_09
Patent number
US07790729B2

Reaction notes

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