2-Pyrazinecarboxylic acid → 5-(2-Cyano-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridin-3-yloxy)-1H-benzimidazole

HRID 13295

Reaction equation

HRID 13295 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7](O)=O.OC1C2N=NNC=2C=CC=1.[H-].CN(C)CCCN=C=NCC.[C:32]([C:34]1[CH:59]=[CH:58][CH:57]=[CH:56][C:35]=1[O:36][C:37]1[CH:38]=[C:39]([NH2:55])[C:40]([NH2:54])=[CH:41][C:42]=1[O:43][C:44]1[CH:45]=[N:46][C:47]([S:50]([CH3:53])(=[O:52])=[O:51])=[CH:48][CH:49]=1)#[N:33]>C(OCC)(=O)C.CN(C)C=O>[C:32]([C:34]1[CH:59]=[CH:58][CH:57]=[CH:56][C:35]=1[O:36][C:37]1[C:42]([O:43][C:44]2[CH:45]=[N:46][C:47]([S:50]([CH3:53])(=[O:51])=[O:52])=[CH:48][CH:49]=2)=[CH:41][C:40]2[NH:54][C:7]([C:2]3[CH:3]=[N:4][CH:5]=[CH:6][N:1]=3)=[N:55][C:39]=2[CH:38]=1)#[N:33]

Participants

7

Reactant 4

HCID 10472-Pyrazinecarboxylic acidHCID 231453124-(2-Cyano-phenoxy)-5-(6-methanesulfonyl-pyridin-3-yloxy)-benzene-1,2-diamineHCID 866192011-(3-Dimethylaminopropyl)-3-ethylcarbodiimide monohydrideHCID 178418300HCID 178418300, compound

Product 1

HCID 231452075-(2-Cyano-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridin-3-yloxy)-1H-benzimidazole

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

21 mg of pyrazine-2-carboxylic acid, 52 mg of hydroxybenzotriazole and 52 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide monohydride were added to a dimethylformamide (2 ml) solution of 72 mg of 4-(2-cyano-phenoxy)-5-(6-methanesulfonyl-pyridin-3-yloxy)-benzene-1,2-diamine obtained in Example 196 (step 5), and the reaction liquid was stirred at room temperature for 1 hour. The reaction liquid was diluted with ethyl acetate, washed with aqueous saturated sodium bicarbonate, water and saturated saline in order, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was dissolved in 1 ml of N-methylpyrrolidinone, and 20 mg of ytterbium trifluoromethanesulfonate was added to it, and the reaction liquid was stirred at 160° C. for 2 h ours. The reaction liquid was diluted with ethyl acetate, washed with aqueous saturated sodium bicarbonate and saturated saline in order, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: chloroform/methanol=30/1) and through partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1) to obtain the entitled compound as a brown solid.

Workup

  1. customthe reaction liquid
  2. customThe reaction liquid
  3. washwashed with aqueous saturated sodium bicarbonate, water and saturated saline in order
  4. dry with materialdried with anhydrous sodium sulfate
  5. customThe solvent was evaporated away under reduced pressure
  6. dissolutionthe resulting residue was dissolved in 1 ml of N-methylpyrrolidinone
  7. addition20 mg of ytterbium trifluoromethanesulfonate was added to it
  8. customthe reaction liquid
  9. stirringwas stirred at 160° C. for 2 h ours
  10. customThe reaction liquid
  11. washwashed with aqueous saturated sodium bicarbonate and saturated saline in order
  12. dry with materialdried with anhydrous sodium sulfate
  13. customThe solvent was evaporated away under reduced pressure
  14. customthe resulting residue was purified through silica gel column chromatography (developing solvent: chloroform/methanol=30/1)
  15. customthrough partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1)

Sources & evidence

ORD record
ord-b0457459d64b4664b6ce4025aaac386e
Source dataset
uspto-grants-2010_06
Patent number
US07728025B2

Linked notes

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