Pyridine → HCID 21959027, compound

HRID 854786Notes

Reaction equation

HRID 854786 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][C:18]2=[O:22])[C:13](O)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.[NH2:29][C:30]1[CH:35]=[N:34][CH:33]=[CH:32][N:31]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][C:18]2=[O:22])[C:13]([NH:29][C:30]2[CH:35]=[N:34][CH:33]=[CH:32][N:31]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]

Participants

8

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 78747AminopyrazineHCID 219590032-[3-Chloro-4-(methanesulfonyl)phenyl]-3-(2-oxocyclopentyl)propanoic acid

Product 1

HCID 21959027HCID 21959027, compoundYield 29.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2(R)-(3-chloro-4-methylsulfonyl-phenyl)-N-methyl-N-(1(R)-methyl-2-oxo-2(R)-phenyl-ethyl)-3-(2-oxo-cyclopentyl)-propionamide (1.29 g, 2.63 mmol) in dioxane (4.43 mL) was treated with an 18M aqueous hydrochloric acid solution (4.43 mL). The reaction was then heated to 120° C. for 18 h. At this time, the reaction was cooled to 25° C., diluted with water (50 mL), and extracted with a 90/10 methylene chloride/methanol solution 3×100 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, ethyl acetate) afforded racemic 2-(3-chloro-4-methylsulfonyl-phenyl)-3-(2-oxo-cyclopentyl)-propionic acid (563.3 mg, 62.1%) as a light tan foam. A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(2-oxo-cyclopentyl)-propionic acid (563.3 mg, 1.6 mmol) in methylene chloride (16.4 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.90 mL, 1.80 mmol) and a few drops of N,N-dimethylformamide. The reaction mixture was stirred at 0° C. for 10 min and at 25° C. for 20 min. The reaction mixture was then treated with a solution of 2-aminopyrazine (342 mg, 3.60 mmol) and pyridine (0.3 mL, 3.60 mmol) in tetrahydrofuran (8.2 mL). This solution was stirred at 25° C. for 18 h. At this time, the reaction was concentrated in vacuo. The residue was dissolved in methylene chloride (100 mL) and washed with a 1N aqueous hydrochloric acid solution (2×100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 75/25 ethyl acetate/hexanes) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(2-oxo-cyclopentyl)-N-pyrazin-2-yl-propionamide (198.8 mg, 28.9%) as a clear oil.

Workup

  1. stirringThis solution was stirred at 25° C. for 18 h
  2. concentrationAt this time, the reaction was concentrated in vacuo
  3. dissolutionThe residue was dissolved in methylene chloride (100 mL)
  4. washwashed with a 1N aqueous hydrochloric acid solution (2×100 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1551d9428a9f4c31a0593920a90ad537
Source dataset
uspto-grants-2007_08
Patent number
US07259166B2

Reaction notes

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