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

HRID 720000Notes

Reaction equation

HRID 720000 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].[S:49]1[CH:53]=[CH:52][CH:51]=[C:50]1[C:54]1[N:55]=[CH:56][C:57]([NH2:60])=[N:58][CH:59]=1.N1C=CC=CC=1>C(Cl)Cl>[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]([NH:60][C:57]2[CH:56]=[N:55][C:54]([C:50]3[S:49][CH:53]=[CH:52][CH:51]=3)=[CH:59][N:58]=2)=[O:42])[CH:32]=[CH:33][C:34]=1[S:35]([CH3:38])(=[O:36])=[O:37]

Participants

7

Reactant 5

HCID 1049PyridineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 116440152-Pyrazinamine, 5-(2-thienyl)-HCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acid

Product 1

HCID 117552962(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-thiophen-2-yl-pyrazin-2-yl)-propionamideYield 58.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (230.0 mg, 0.877 mmol) in methylene chloride (15 mL) cooled to 0° C. was treated with N-bromosuccinimide (160.0 mg, 0.899 mmol). The reaction mixture was stirred at 0° C. for 5 min and then treated with 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 232.0 mg, 0.701 mmol). The reaction mixture was allowed to warm to 25° C. over 15 min. The reaction mixture was then treated with 5-thiophen-2-yl-pyrazin-2-ylamine (260.0 mg, 1.467 mmol) followed by pyridine (0.24 mL, 2.967 mmol). The resulting reaction mixture was stirred at 25° C. for 1 h. The reaction mixture was then diluted with methylene chloride and washed with a dilute aqueous hydrochloric acid solution. The aqueous layer was back-extracted with methylene chloride. The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution and water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 3/1 to 3/2 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-thiophen-2-yl-pyrazin-2-yl)-propionamide (202.3 mg, 58.9%) as a yellow foam: mp 97–99° C. (foam to gel); (ES)+-HRMS m/e calcd for C23H24ClN3O3S2 (M+H)+ 490.1021, found 490.1026.

Workup

  1. temperatureto warm to 25° C. over 15 min
  2. customThe resulting reaction mixture
  3. stirringwas stirred at 25° C. for 1 h
  4. washwashed with a dilute aqueous hydrochloric acid solution
  5. extractionThe aqueous layer was back-extracted with methylene chloride
  6. washThe combined organic layers were washed with a saturated aqueous sodium bicarbonate solution and water
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-faf0afdb09194dda8b18f7a27ac5f4d5
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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