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

HRID 719863Notes

Reaction equation

HRID 719863 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[Cl:28][C:29]1[CH:30]=[C:31]([C@@H:39]([CH2:43][CH:44]2[CH2:48][CH2:47][CH2:46][CH2:45]2)[C:40]([OH:42])=O)[CH:32]=[CH:33][C:34]=1[S:35]([CH3:38])(=[O:37])=[O:36].[NH2:49][C:50]1[CH:55]=[N:54][C:53]([Br:56])=[CH:52][N:51]=1.N1C=CC=CC=1>C(Cl)Cl>[Br:56][C:53]1[N:54]=[CH:55][C:50]([NH:49][C:40](=[O:42])[C@@H:39]([C:31]2[CH:32]=[CH:33][C:34]([S:35]([CH3:38])(=[O:36])=[O:37])=[C:29]([Cl:28])[CH:30]=2)[CH2:43][CH:44]2[CH2:48][CH2:47][CH2:46][CH2:45]2)=[N:51][CH:52]=1

Participants

7

Reactant 5

HCID 1049PyridineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 5995392-Amino-5-bromopyrazineHCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acid

Product 1

HCID 86593779N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamideYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A stirred solution of triphenylphosphine (8.57 g, 32.6 mmol) in anhydrous methylene chloride (110 mL) under nitrogen at 0° C. was treated with N-bromosuccinimide (5.80 g, 32.6 mmol). After 15 min, 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 9.00 g, 27.2 mmol) was added to the reaction. The mixture was allowed to warm to 25° C. After stirring at 25° C. for 10 min, the reaction was treated with 2-amino-5-bromopyrazine (7.92 g, 45.6 mmol) followed by pyridine (8.79 mL, 108.8 mmol). The mixture was allowed to stir at 25° C. for 1.5 h. At this time, the reaction was diluted with methylene chloride and then was washed with a 1N aqueous hydrochloric acid solution (200 mL) followed by a 10% aqueous potassium carbonate solution (100 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70–230 mesh, 3/7 ethyl acetate/hexanes) afforded N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (10.02 g, 76%) as a white foam: mp 77–82° C. (foam to gel); (ES)+-HRMS m/e calcd for C19H21BrClN3O3S (M+H)+ 486.0249, found 486.0255.

Workup

  1. stirringto stir at 25° C. for 1.5 h
  2. washwas washed with a 1N aqueous hydrochloric acid solution (200 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b73673d83789407ca5e2183cbfb12887
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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