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

HRID 418681Notes

Reaction equation

HRID 418681 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 39.1%

Reagents, catalysts & solvents 3

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

Procedure

To a mixture of 1-methyl-1,2,3,6-tetrahydropyridin-4-yl trifluoromethanesulfonate 257 (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 down and filtered. To the filtrate containing the intermediate 258 were added bromide 50 (435 mg, 1.84 mmol), 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 2 h more. The reaction mixture was diluted with water and extracted with DCM; the organic phase was extracted with 1N HCl, the aqueous phase basified to pH-11 by addition of 2N aqueous NaOH, extracted with DCM, dried over anhydrous Na2SO4 and concentrated under reduced pressure affording 259 (279 mg, 0.72 mmol, 39% yield) as a brown solid. MS (m/z): (M+1) 385.9 (100%).

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 down
  5. filtrationfiltered
  6. additionTo the filtrate containing the intermediate 258
  7. temperaturethe mixture was heated
  8. temperatureto reflux for 2 h more
  9. extractionextracted with DCM
  10. extractionthe organic phase was extracted with 1N HCl
  11. additionthe aqueous phase basified to pH-11 by addition of 2N aqueous NaOH
  12. extractionextracted with DCM
  13. dry with materialdried over anhydrous Na2SO4
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-428b9b7e7f8b4fb1b23d389b99b7c5a4
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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