2-Pyrazinecarboxylic acid → 2,2,2-trifluoro-1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-3H-benzimidazol-5-yl)-pyrrolidin-1-yl)-ethanone

HRID 13339Notes

Reaction equation

HRID 13339 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7](O)=O.Cl.CN(C)CCCN=C=NCC.N1C=CC=CC=1.[F:28][C:29]([F:64])([F:63])[C:30]([N:32]1[CH2:36][CH2:35][CH2:34][CH:33]1[C:37]1[C:51]([O:52][C:53]2[CH:58]=[CH:57][C:56]([S:59]([CH3:62])(=[O:61])=[O:60])=[CH:55][CH:54]=2)=[CH:50][C:40]2[N:41]=C(C3C=CC=CN=3)[NH:43][C:39]=2[CH:38]=1)=[O:31]>C(OCC)(=O)C>[F:64][C:29]([F:28])([F:63])[C:30]([N:32]1[CH2:36][CH2:35][CH2:34][CH:33]1[C:37]1[C:51]([O:52][C:53]2[CH:58]=[CH:57][C:56]([S:59]([CH3:62])(=[O:61])=[O:60])=[CH:55][CH:54]=2)=[CH:50][C:40]2[N:41]=[C:7]([C:2]3[CH:3]=[N:4][CH:5]=[CH:6][N:1]=3)[NH:43][C:39]=2[CH:38]=1)=[O:31]

Participants

6

Reactant 4

HCID 10472-Pyrazinecarboxylic acidHCID 1049PyridineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 231457212,2,2-trifluoro-1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyridin-2-yl-3H-benzimidazol-5-yl)-pyrrolidin-1-yl)-ethanone

Product 1

HCID 231455992,2,2-trifluoro-1-(2-(6-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-3H-benzimidazol-5-yl)-pyrrolidin-1-yl)-ethanone

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

14.5 mg of pyrazine-2-carboxylic acid and 27.0 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide monohydrochloride were added in order to a pyridine (1 ml) solution of 53 mg of 1-(2-(4,5-diamino-2-(4-methanesulfonyl-phenoxy)-phenyl)-pyrrolidin-1-yl)-2,2,2-trifluoro-ethanone obtained in Example 162 (step 6), and the reaction liquid was stirred at room temperature for 3 hours. The reaction liquid was diluted with saturated saline, and extracted with ethyl acetate. The organic layers were combined, washed with aqueous saturated ammonium chloride and aqueous saturated sodium bicarbonate in order, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was dissolved in 1 ml of toluene. 9.9 mg of p-toluenesulfonic acid monohydrate was added to it, and the reaction liquid was stirred at 120° C. for 6 hours. After cooled, the reaction liquid was diluted with ethyl acetate, washed with aqueous saturated sodium bicarbonate and saturated saline in order, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure, and the residue was purified through partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=9/1) to obtain the entitled compound as an oily substance.

Workup

  1. customthe reaction liquid
  2. customThe reaction liquid
  3. additionwas diluted with saturated saline
  4. extractionextracted with ethyl acetate
  5. washwashed with aqueous saturated ammonium chloride and aqueous saturated sodium bicarbonate in order
  6. dry with materialdried with anhydrous magnesium sulfate
  7. customThe solvent was evaporated away under reduced pressure
  8. dissolutionthe resulting residue was dissolved in 1 ml of toluene
  9. addition9.9 mg of p-toluenesulfonic acid monohydrate was added to it
  10. customthe reaction liquid
  11. stirringwas stirred at 120° C. for 6 hours
  12. temperatureAfter cooled
  13. customthe reaction liquid
  14. washwashed with aqueous saturated sodium bicarbonate and saturated saline in order
  15. dry with materialdried with anhydrous magnesium sulfate
  16. customThe solvent was evaporated away under reduced pressure
  17. customthe residue was purified
  18. customthrough partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=9/1)
  19. customto obtain the entitled compound as an oily substance

Sources & evidence

ORD record
ord-e2d067810a9a4f659b1ee89b1ee9e2ba
Source dataset
uspto-grants-2010_06
Patent number
US07728025B2

Reaction notes

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