Aniline → 5-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(6-ethanesulfonyl-pyridin-3-yloxy)-1H-benzimidazole

HRID 13308

Reaction equation

HRID 13308 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C(=O)([O-])[O-].[K+].[K+].F[C:17]1[C:18]([O:27][C:28]2[CH:29]=[N:30][C:31]([S:34]([CH2:37][CH3:38])(=[O:36])=[O:35])=[CH:32][CH:33]=2)=[CH:19][C:20]([N+:24]([O-])=O)=[C:21]([NH2:23])[CH:22]=1.O.NN.[NH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.N1C=CC=CC=1C=O>[Ni].CO.O.CN1CCCC1=O>[C:4]([C:3]1[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=1[O:1][C:17]1[C:18]([O:27][C:28]2[CH:29]=[N:30][C:31]([S:34]([CH2:37][CH3:38])(=[O:36])=[O:35])=[CH:32][CH:33]=2)=[CH:19][C:20]2[NH:24][C:48]([C:47]3[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=3)=[N:23][C:21]=2[CH:22]=1)#[N:5]

Participants

11

Reactant 6

HCID 6115AnilineHCID 11430Potassium CarbonateHCID 119072-HydroxybenzonitrileHCID 142732-PyridinecarboxaldehydeHCID 24654Hydrazine hydrate (1:1)HCID 231450955-Fluoro-4-(6-ethanesulfonyl-pyridin-3-yloxy)-2-nitro-phenylamine

Product 1

HCID 113754065-(2-cyano-phenoxy)-2-pyridin-2-yl-6-(6-ethanesulfonyl-pyridin-3-yloxy)-1H-benzimidazole

Reagents, catalysts & solvents 4

HCID 935NickelCatalystHCID 887MethanolSolvent3×HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
90 °C

Procedure

60 mg of 2-hydroxy-benzonitrile and 70 mg of potassium carbonate were added to an N-methylpyrrolidinone (3 ml) solution of 150 mg of 5-fluoro-4-(6-ethanesulfonyl-pyridin-3-yloxy)-2-nitro-phenylamine, and the reaction liquid was stirred at 90° C. for 5 hours. Water was added to the reaction liquid, and the deposit was taken out through filtration to obtain a crude product. 10 mg of developed Raney nickel and 0.12 ml of hydrazine monohydrate were added to a methanol (5 ml) solution of the resulting crude product, and the reaction liquid was stirred for 1 hour. The catalyst was removed through filtration, and the solvent was evaporated away under reduced pressure to obtain 160 mg of a crude product. 0.20 ml of 1 M methanol solution of aniline and pyridine-2-carboxaldehyde (1/1) was added to a methanol (3 ml) solution of 35 mg of the resulting crude product, and the reaction liquid was stirred overnight at 80° C. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1) to obtain the entitled compound as a yellow solid.

Workup

  1. customthe reaction liquid
  2. filtrationthe deposit was taken out through filtration
  3. customto obtain a crude product
  4. customthe reaction liquid
  5. stirringwas stirred for 1 hour
  6. customThe catalyst was removed through filtration
  7. customthe solvent was evaporated away under reduced pressure
  8. customto obtain 160 mg of a crude product
  9. customthe reaction liquid
  10. stirringwas stirred overnight at 80° C
  11. customThe solvent was evaporated away under reduced pressure
  12. customthe resulting residue was purified
  13. customthrough partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=15/1)

Sources & evidence

ORD record
ord-b879c2a91b2e4143b6365f1c1d108198
Source dataset
uspto-grants-2010_06
Patent number
US07728025B2

Linked notes

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