Triethylamine → 2-Chloro-5-[(3-chloropyridin-4-yl)(2,5-difluorophenyl)methylthio]pyridine

HRID 2080418Notes

Reaction equation

HRID 2080418 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[CH:8]([C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1[F:17])O.C(N(CC)CC)C.CS(Cl)(=O)=O.[Cl:30][C:31]1[N:36]=[CH:35][C:34]([SH:37])=[CH:33][CH:32]=1.C(=O)([O-])[O-].[K+].[K+]>CCCCCC.C(OCC)(=O)C.CN(C)C=O.ClCCl>[Cl:30][C:31]1[CH:32]=[CH:33][C:34]([S:37][CH:8]([C:7]2[CH:6]=[CH:5][N:4]=[CH:3][C:2]=2[Cl:1])[C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[F:17])=[CH:35][N:36]=1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 14158786-Chloropyridine-3-thiolHCID 231146543-Chloro-4-[(2,5-difluorophenyl)-hydroxymethyl]pyridine

Product 1

HCID 231147932-Chloro-5-[(3-chloropyridin-4-yl)(2,5-difluorophenyl)methylthio]pyridineYield 48%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a dichloromethane (3 ml) solution of the 3-chloro-4-[(2,5-difluorophenyl)-hydroxymethyl]pyridine (153 mg, 0.60 mmol) obtained in Referential Example 23 were added triethylamine (0.167 ml, 1.20 mmol) and methanesulfonyl chloride (0.070 ml, 0.90 mmol) sequentially at 0° C. The resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was washed with a saturated aqueous solution of sodium bicarbonate. The organic layer was then dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. To an N,N-dimethylformamide (3 ml) solution of the residue thus obtained was added an N,N-dimethylformamide (2 ml) solution of 6-chloro-3-pyridinethiol and potassium carbonate (100 mg, 0.72 mmol) sequentially. The resulting mixture was stirred at room temperature for 18 hours. Ethyl acetate was added to the reaction mixture. The resulting mixture was washed with a saturated aqueous solution of sodium bicarbonate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue thus obtained was subjected to flash silica gel chromatography. The fraction obtained from the hexane:ethyl acetate=17:3 eluate was concentrated under reduced pressure to give the title compound (111 mg, 0.29 mmol, 48%) as a white solid.

Workup

  1. washThe reaction mixture was washed with a saturated aqueous solution of sodium bicarbonate
  2. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customTo an N,N-dimethylformamide (3 ml) solution of the residue thus obtained
  6. stirringThe resulting mixture was stirred at room temperature for 18 hours
  7. washThe resulting mixture was washed with a saturated aqueous solution of sodium bicarbonate
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customThe residue thus obtained
  12. concentrationethyl acetate=17:3 eluate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-11f3330bd86142a190edd11c301da7af
Source dataset
uspto-grants-2011_04
Patent number
US07932271B2

Reaction notes

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