Benzyl Alcohol → 4-((6-(benzyloxy)-3-fluoropyridin-2-ylamino)methyl)tetrahydro-2H-pyran-4-carbonitrile

HRID 1963838Notes

Reaction equation

HRID 1963838 reaction equation
[CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[F:11][C:12]1[C:13]([NH:19][CH2:20][C:21]2([C:27]#[N:28])[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[N:14][C:15](F)=[CH:16][CH:17]=1>CN(C=O)C.[Cl-].[Na+].O>[CH2:1]([O:8][C:15]1[N:14]=[C:13]([NH:19][CH2:20][C:21]2([C:27]#[N:28])[CH2:22][CH2:23][O:24][CH2:25][CH2:26]2)[C:12]([F:11])=[CH:17][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 581273494-((3,6-difluoropyridin-2-ylamino)methyl)tetrahydro-2H-pyran-4-carbonitrile

Product 1

HCID 581272084-((6-(benzyloxy)-3-fluoropyridin-2-ylamino)methyl)tetrahydro-2H-pyran-4-carbonitrileYield 66%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
90 °C

Procedure

Benzyl alcohol (352 mg, 3.26 mmol) was dissolved in anhydrous DMF (2 ml) and placed under argon. This was then treated with a 60% dispersion in oil of SODIUM HYDRIDE (78.7 mg, 3.26 mmol). This resultant suspension was then stirred at room temperature for 15 min. At this time it was treated with a solution of 4-((3,6-difluoropyridin-2-ylamino)methyl)tetrahydro-2H-pyran-4-carbonitrile (275 mg, 1.09 mmol) dissolved in anhydrous DMF (2 ml). Once the addition was complete the reaction was stirred at 90° C. for 5 hours. The reaction was allowed to cool to room temperature. It was then poured into brine (20 ml). This was extracted with EtOAc (3×15 ml). The combined extracts were washed with H2O (3×10 ml) followed by brine (1×10 ml). The organic layer was dried (Na2SO4), filtered, and the solvent removed in vacuo to give the crude material which was purified using the ISCO and a 12 g SiO2 column. Eluted using 100 hexanes to 30 EtOAc/70 hexanes over 20 min. 245 mg (66% yield) of the desired product was obtained as a viscous liquid. LCMS (m/z): 342.1 [M+H]+; retention time=1.017 min.

Workup

  1. additionOnce the addition
  2. temperatureto cool to room temperature
  3. extractionThis was extracted with EtOAc (3×15 ml)
  4. washThe combined extracts were washed with H2O (3×10 ml)
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customto give the crude material which
  9. customwas purified
  10. washEluted
  11. customover 20 min

Sources & evidence

ORD record
ord-69f7d1a6a5f5464e877b7e0a15955d0b
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

Loading…