Pyridine → HCID 10481771, compound

HRID 719980Notes

Reaction equation

HRID 719980 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.[NH2:28][C:29]1[N:30]=[CH:31][C:32]([C:35]2([CH3:42])[NH:39][C:38](=[O:40])[NH:37][C:36]2=[O:41])=[N:33][CH:34]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([NH:28][C:29]2[CH:34]=[N:33][C:32]([C:35]3([CH3:42])[C:36](=[O:41])[NH:37][C:38](=[O:40])[NH:39]3)=[CH:31][N:30]=2)=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

8

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acidHCID 21897288HCID 21897288, compound

Product 1

HCID 10481771HCID 10481771, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 200 mg, 0.606 mmol) in methylene chloride (5 mL) was treated with oxalyl chloride (116 μL, 1.212 mmol) and N,N-dimethylformamide (1 drop). The mixture was stirred at 25° C. for 1 h. The reaction mixture was concentrated in vacuo, and the residue was dried in vacuo. The residue was then dissolved in benzene, and the solvents were concentrated in vacuo. The residue was dried in vacuo. This material was dissolved in methylene chloride (5 mL), cooled to 0° C., and then treated with a mixture of 5-(5-amino-pyrazin-2-yl)-5-methyl-imidazolidine-2,4-dione (150 mg, 0.727 mmol) and pyridine (98 μL) in methylene chloride (1 mL) and dimethyl sulfoxide (1 mL). The ice bath was removed, and the solution was stirred at 25° C. overnight. The reaction mixture was concentrated in vacuo and then extracted with ethyl acetate and a 0.1N aqueous hydrochloric acid solution. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 1/4 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(4-methyl-2,5-dioxo-imidazolidin-4-yl)-pyrazin-2-yl]-propionamide (82 mg, 26%) as a light yellow solid: (ES)+-HRMS m/e calcd for C23H26ClN5O5S (M+H)+ 520.1416, found 520.1403.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was dried in vacuo
  3. dissolutionThe residue was then dissolved in benzene
  4. concentrationthe solvents were concentrated in vacuo
  5. customThe residue was dried in vacuo
  6. dissolutionThis material was dissolved in methylene chloride (5 mL)
  7. temperaturecooled to 0° C.
  8. customThe ice bath was removed
  9. stirringthe solution was stirred at 25° C. overnight
  10. concentrationThe reaction mixture was concentrated in vacuo
  11. extractionextracted with ethyl acetate
  12. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-02ee6f8682c74096a130e1253baf1dab
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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