N-methyl-2-pyrrolidone → HCID 178437679, compound

HRID 869269Notes

Reaction equation

HRID 869269 reaction equation
Cl[C:2]1[C:3]([C:11]([NH2:13])=[O:12])=[N:4][C:5]([CH2:9][CH3:10])=[C:6](Cl)[N:7]=1.[Cl:14][C:15]1[CH:16]=[C:17]([CH:19]=[CH:20][C:21]=1[S:22]([CH3:25])(=[O:24])=[O:23])[NH2:18].CN1C(=O)CCC1.[NH2:33][C@H:34]1[CH2:39][CH2:38][C@H:37]([OH:40])[CH2:36][CH2:35]1>C(OCC)(=O)C.C(O)C>[Cl:14][C:15]1[CH:16]=[C:17]([NH:18][C:2]2[C:3]([C:11]([NH2:13])=[O:12])=[N:4][C:5]([CH2:9][CH3:10])=[C:6]([NH:33][C@H:34]3[CH2:39][CH2:38][C@H:37]([OH:40])[CH2:36][CH2:35]3)[N:7]=2)[CH:19]=[CH:20][C:21]=1[S:22]([CH3:25])(=[O:24])=[O:23]

Participants

7

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 108459213-Chloro-4-methanesulfonylanilineHCID 848199603,5-Dichloro-6-ethylpyrazine-2-carboxamideHCID 178511715HCID 178511715, compound

Product 1

HCID 178437679HCID 178437679, compoundYield 9.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
230 °C

Procedure

A mixture of 3,5-dichloro-6-ethylpyrazine-2-carboxamide (200 mg), 3-chloro-4-methylsulfonylaniline (374 mg) and NMP (1 mL) was stirred at 230° C. for 1 hour using a microwave reaction system. Thereafter, trans-4-aminocyclohexanol (524 mg) was added to the reaction liquid and stirred at 190° C. for 30 minutes using a microwave reaction system. After cooling, the reaction liquid was partitioned using ethyl acetate and water, and the organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride. After drying over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (eluent; chloroform:methanol=10:0 to 30:1) to give a crude product. This product was heated with ethanol and washed to give a light yellow solid. To the light yellow solid, ethyl acetate was added and heated, and insoluble materials were separated by filtration and the filtrate was concentrated. After the filtrate was concentrated, the residue was heated and washed with ethanol to give 3-{[3-chloro-4-(methylsulfonyl)phenyl]amino}-6-ethyl-5-[(trans-4-hydroxycyclohexyl)amino]pyrazine-2-carboxamide (39 mg) as a light yellow solid.

Workup

  1. customa microwave reaction system
  2. stirringstirred at 190° C. for 30 minutes
  3. customa microwave reaction system
  4. temperatureAfter cooling
  5. customthe reaction liquid
  6. customwas partitioned
  7. washthe organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride
  8. dry with materialAfter drying over anhydrous magnesium sulfate
  9. distillationthe solvent was distilled off
  10. customthe residue was purified by silica gel column chromatography (eluent; chloroform:methanol=10:0 to 30:1)
  11. customto give a crude product
  12. washwashed
  13. customto give a light yellow solid
  14. temperatureheated
  15. custominsoluble materials were separated by filtration
  16. concentrationthe filtrate was concentrated
  17. concentrationAfter the filtrate was concentrated
  18. temperaturethe residue was heated
  19. washwashed with ethanol

Sources & evidence

ORD record
ord-fface636fc744497a68fab8ccd0e5bbc
Source dataset
uspto-grants-2015_03
Patent number
US08969336B2

Reaction notes

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