Dimethylformamide → 6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-nicotinonitrile

HRID 1766772Notes

Reaction equation

HRID 1766772 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:9][CH:10]([C:12]2[C:17]([Cl:18])=[CH:16][CH:15]=[C:14]([F:19])[C:13]=2[Cl:20])[CH3:11])[C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:21][N:22](C=O)C>O.[C-]#N.[C-]#N.[Zn+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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[NH2:8][C:5]1[C:4]([O:9][CH:10]([C:12]2[C:17]([Cl:18])=[CH:16][CH:15]=[C:14]([F:19])[C:13]=2[Cl:20])[CH3:11])=[CH:3][C:2]([C:21]#[N:22])=[CH:7][N:6]=1

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 211114785-Bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine

Product 1

HCID 211113376-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-nicotinonitrileYield 97%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-bromo-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine (5.00 g, 13.15 mmol) in DMF (73 mL) and water (1 mL) was added Zn(CN)2 (4.50 g, 26.3 mmol), Pd2(dba)3 (0.602 g, 0.65 mmol), and DPPF (0.86 g, 1.55 mmol). The mixture was degassed and charged with nitrogen for three time, and then stirred under nitrogen at 100° C. for 3 hr. The reaction solution was partitioned between ethyl acetate and water. The organic layer was washed with a solution of sat. NH4Cl-conc. NH4OH-water (4:1:4), then dried over MgSO4. The crude product was purified on a silica gel column eluting with ethyl acetate-hexanes (1:4) to provide 6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-nicotinonitrile as a white solide (4.15 g, 97% yield).

Workup

  1. customThe mixture was degassed
  2. additioncharged with nitrogen for three time
  3. customThe reaction solution was partitioned between ethyl acetate and water
  4. washThe organic layer was washed with a solution of sat. NH4Cl-conc
  5. dry with materialNH4OH-water (4:1:4), then dried over MgSO4
  6. customThe crude product was purified on a silica gel column
  7. washeluting with ethyl acetate-hexanes (1:4)

Sources & evidence

ORD record
ord-7ff06db9a95c42e3acdd2433e8f88d37
Source dataset
uspto-grants-2007_06
Patent number
US07230098B2

Reaction notes

Loading…