Cesium carbonate → cyclobutyl (S)-4-acetyl-3-methyl-7-(1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-carboxylate

HRID 1485715Notes

Reaction equation

HRID 1485715 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10](Br)=[CH:11][CH:12]=2)[N:7]([C:15]([O:17][CH:18]2[CH2:21][CH2:20][CH2:19]2)=[O:16])[CH2:6][C@@H:5]1[CH3:22])(=[O:3])[CH3:2].CC1(C)OB([C:29]2[CH:30]=[N:31][N:32](C(OC(C)(C)C)=O)[CH:33]=2)OC1(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>C(OCC)(=O)C.O>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:29]3[CH:30]=[N:31][NH:32][CH:33]=3)=[CH:11][CH:12]=2)[N:7]([C:15]([O:17][CH:18]2[CH2:21][CH2:20][CH2:19]2)=[O:16])[CH2:6][C@@H:5]1[CH3:22])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 118080227(S)-cyclobutyl 4-acetyl-7-bromo-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate

Product 1

HCID 118080491cyclobutyl (S)-4-acetyl-3-methyl-7-(1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-carboxylateYield 62.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A 500-mL round-bottom flask was purged with nitrogen and charged with cyclobutyl (S)-4-acetyl-7-bromo-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate (15.0 g, 40.9 mmol), tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (20 g, 68 mmol), cesium carbonate (40.0 g, 123 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (2.0 g, 2.45 mmol), 1,4-dioxane (150 mL), and water (15 mL). The resulting mixture was stirred overnight at 100° C. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (200 mL) and washed with water (100 mL). The combined organic phases were washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 1:3, ethyl acetate/petroleum ether) to afford cyclobutyl (S)-4-acetyl-3-methyl-7-(1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-carboxylate (9.0 g, 62%) of as a yellow solid. MS (ESI, pos. ion) m/z 355 [M+H]+.

Workup

  1. customA 500-mL round-bottom flask was purged with nitrogen
  2. temperatureAfter cooling to room temperature
  3. washwashed with water (100 mL)
  4. washThe combined organic phases were washed with brine (100 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified via column chromatography on silica gel (eluting with 1:3, ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-e3c62fcb02c349e69c11aaa26f6b8f8d
Source dataset
uspto-grants-2016_08
Patent number
US09422281B2

Reaction notes

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