Pyridine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-methanesulfonylamino-pyridin-2-yl)-propionamide

HRID 719870Notes

Reaction equation

HRID 719870 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:34]=[CH:33][C:32]([NH:35][S:36]([CH3:39])(=[O:38])=[O:37])=[CH:31][CH:30]=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:30]=[CH:31][C:32]([NH:35][S:36]([CH3:39])(=[O:38])=[O:37])=[CH:33][N:34]=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 21897349N-(6-aminopyridin-3-yl)methanesulfonamide

Product 1

HCID 100289202(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-methanesulfonylamino-pyridin-2-yl)-propionamideYield 10.3%

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, 224 mg, 0.67 mmol) in methylene chloride was cooled to 0° C. and then was treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.37 mL, 0.74 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 N-(6-amino-pyridin-3-yl)-methanesulfonamide (190 mg, 1.01 mmol) and pyridine (0.08 mL, 1.01 mmol) in tetrahydrofuran (3.38 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 the organic layer 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 then dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 3/1 ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-methanesulfonylamino-pyridin-2-yl)-propionamide (34.4 mg, 10.2%) as a light tan solid: mp 146–150° C.; EI-HRMS m/e calcd for C21H26ClN3O5S2 (M+H)+ 500.1075, found 500.1081.

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

Sources & evidence

ORD record
ord-79d697042db94c3091c797a04310b4fb
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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