Pyridine → HCID 86593786, compound

HRID 719899Notes

Reaction equation

HRID 719899 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:25][CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)[C:13]([NH:15][C:16]2[N:17]=[CH:18][C:19]([C:22](O)=[O:23])=[N:20][CH:21]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.Cl.[O:38](ON)[C:39]([CH3:42])([CH3:41])[CH3:40].[N:45]1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.O1CCCC1>[C:39]([O:38][NH:45][C:22]([C:19]1[CH:18]=[N:17][C:16]([NH:15][C:13](=[O:14])[C@@H:12]([C:4]2[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[C:2]([Cl:1])[CH:3]=2)[CH2:25][CH:26]2[CH2:27][CH2:28][CH2:29][CH2:30]2)=[CH:21][N:20]=1)=[O:23])([CH3:42])([CH3:41])[CH3:40]

Participants

8

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 21897322HCID 21897322, compoundHCID 67482613HCID 67482613, compound

Product 1

HCID 86593786HCID 86593786, compoundYield 73%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 5-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazine-2-carboxylic acid (401.6 mg, 0.889 mmol) in methylene chloride (4.4 mL) was cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (310 μL, 3.554 mmol) and N,N-dimethylformamide (2 drops). The reaction mixture was stirred at 0° C. for 45 min and then slowly warmed to 25° C. over 1 h 45 min. The solution was then concentrated in vacuo. The residue was dissolved in methylene chloride (3.4 mL) and cooled to 0° C. The resulting solution was then treated with a mixture of O-(tert-butoxyl)hydroxylamine hydrochloride (133.3 mg, 1.061 mmol) and pyridine (180 μL, 2.226 mmol) in tetrahydrofuran (4.4 mL), followed by a methylene chloride rinse (1 mL). The reaction mixture was stirred at 0° C. for 45 min and then stirred at 25° C. for 2 h 15 min. The reaction was then quenched with water (5 mL) and stirred at 25° C. for 30–45 min. The reaction was partitioned between ethyl acetate (300 mL) and a 1N aqueous citric acid solution (250 mL), and the layers were seperated. The organic layer was washed with a saturated aqueous sodium bicarbonate solution (250 mL), water (250 mL), and a saturated aqueous sodium chloride solution (250 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40L, Silica, 2/3 to 1/1 ethyl acetate/hexanes) afforded 5-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazine-2-carboxylic acid tert-butoxy-amide (338.8 mg, 73%) as an off-white foam: mp 128–131° C. (foam to gel); (ES)+-HRMS m/e calcd for C24H31ClN4O5S (M+H)+ 523.1777, found 523.1782.

Workup

  1. temperatureslowly warmed to 25° C. over 1 h 45 min
  2. concentrationThe solution was then concentrated in vacuo
  3. dissolutionThe residue was dissolved in methylene chloride (3.4 mL)
  4. temperaturecooled to 0° C
  5. washrinse (1 mL)
  6. stirringThe reaction mixture was stirred at 0° C. for 45 min
  7. stirringstirred at 25° C. for 2 h 15 min
  8. customThe reaction was then quenched with water (5 mL)
  9. stirringstirred at 25° C. for 30–45 min
  10. customThe reaction was partitioned between ethyl acetate (300 mL)
  11. customa 1N aqueous citric acid solution (250 mL), and the layers were seperated
  12. washThe organic layer was washed with a saturated aqueous sodium bicarbonate solution (250 mL), water (250 mL)
  13. dry with materiala saturated aqueous sodium chloride solution (250 mL), dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3fe0c32baff44bd68a20397719d02d0c
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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