Pyridine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclo-pentyl-N-(5-methanesulfonylamino-pyrazin-2-yl)-propionamide

HRID 719873Notes

Reaction equation

HRID 719873 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]([NH:35][S:36]([CH3:39])(=[O:38])=[O:37])=[N:33][CH:34]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.O1CCCC1>[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]([NH:35][S:36]([CH3:39])(=[O:38])=[O:37])=[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 21897393HCID 21897393, compound

Product 1

HCID 103912912(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclo-pentyl-N-(5-methanesulfonylamino-pyrazin-2-yl)-propionamideYield 5.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 482 mg, 1.45 mmol) in methylene chloride (14.6 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.80 mL, 1.60 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 30 min. The reaction mixture was then treated with a solution of N-(5-amino-pyrazin-2-yl)-methanesulfonamide (548.8 mg, 2.91 mmol) and pyridine (0.24 mL, 2.91 mmol) in tetrahydrofuran (7.29 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 (50 mL) and was washed consecutively with a 1N aqueous hydrochloric acid solution (1×100 mL) and a saturated aqueous sodium bicarbonate solution (1×100 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 95/5 methylene chloride/methanol) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclo-pentyl-N-(5-methanesulfonylamino-pyrazin-2-yl)-propionamide (43.0 mg, 5.9%) as an off-white solid: mp 108–110° C.; EI-HRMS m/e calcd for C20H25ClN4O5S2 (M+H)+ 501.1028, found 501.1031.

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 (50 mL)
  4. washwas washed consecutively with a 1N aqueous hydrochloric acid solution (1×100 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4091804f62634b8c869a887e580ef245
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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