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

HRID 1766772노트

반응식

HRID 1766772 반응식
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

참가 물질

7

반응물 2

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

생성물 1

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

시약·촉매·용매 4

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매

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온도
100 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-7ff06db9a95c42e3acdd2433e8f88d37
출처 데이터셋
uspto-grants-2007_06
특허 번호
US07230098B2

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