Pyridine → HCID 67482855, compound

HRID 719897Notes

Reaction equation

HRID 719897 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.[C:28]([O:32][C:33]([C:35]1[CH:40]=[N:39][C:38]([NH2:41])=[CH:37][N:36]=1)=[O:34])([CH3:31])([CH3:30])[CH3:29].N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.O1CCCC1>[C:28]([O:32][C:33]([C:35]1[CH:40]=[N:39][C:38]([NH:41][C:13](=[O:15])[C@@H:12]([C:4]2[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:9])=[O:10])=[C:2]([Cl:1])[CH:3]=2)[CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[CH:37][N:36]=1)=[O:34])([CH3:31])([CH3:29])[CH3:30]

Participants

8

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acidHCID 45089062HCID 45089062, compound

Product 1

HCID 67482855HCID 67482855, compoundYield 52.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 1.00 g, 3.02 mmol) in methylene chloride (15 mL) was cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (1.10 mL, 12.61 mmol) and N,N-dimethylformamide (2 drops). The reaction mixture was stirred at 0° C. for 30 min and then slowly warmed to 25° C. over 45 min. The solution was then concentrated in vacuo. The yellow slurry was dissolved in methylene chloride (15 mL) and then cooled to 0° C. To this solution was added a solution of 5-amino-pyrazine-2-carboxylic acid tert-butyl ester (0.71 g, 3.64 mmol) and pyridine (295 μL, 3.65 mmol) in tetrahydrofuran (15 mL). The reaction mixture was stirred at 0° C. and was slowly warmed to 25° C. overnight. The reaction was then quenched with a 1N aqueous citric acid solution (10 mL), stirred at 25° C. for 3 min, and then concentrated in vacuo. The reaction material was partitioned between ethyl acetate (400 mL) and a 1N aqueous citric acid solution (200 mL), and the layers were seperated. The organic layer was washed with a saturated aqueous sodium bicarbonate solution (200 mL), water (200 mL), and a saturated aqueous sodium chloride solution (200 mL), dried over sodium sulfate, filtered, and concentrated in vacuo onto silica gel (Merck Silica gel 60, 230–400 mesh). Biotage chromatography (FLASH 40L, Silica, 1/2 ethyl acetate/hexanes) afforded 5-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazine-2-carboxylic acid tert-butyl ester (0.80 g, 52%) as a white foam: mp 107–111° C. (foam to gel); (ES)+-HRMS m/e calcd for C24H30ClN3O5S (M+H)+ 508.1668, found 508.1666.

Workup

  1. temperatureslowly warmed to 25° C. over 45 min
  2. concentrationThe solution was then concentrated in vacuo
  3. dissolutionThe yellow slurry was dissolved in methylene chloride (15 mL)
  4. temperaturecooled to 0° C
  5. stirringThe reaction mixture was stirred at 0° C.
  6. temperaturewas slowly warmed to 25° C. overnight
  7. customThe reaction was then quenched with a 1N aqueous citric acid solution (10 mL)
  8. stirringstirred at 25° C. for 3 min
  9. concentrationconcentrated in vacuo
  10. customThe reaction material was partitioned between ethyl acetate (400 mL)
  11. customa 1N aqueous citric acid solution (200 mL), and the layers were seperated
  12. washThe organic layer was washed with a saturated aqueous sodium bicarbonate solution (200 mL), water (200 mL)
  13. dry with materiala saturated aqueous sodium chloride solution (200 mL), dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo onto silica gel (Merck Silica gel 60, 230–400 mesh)

Sources & evidence

ORD record
ord-6efcb737febe47fd9667f356c5180ab8
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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