Cesium carbonate → HCID 118080563, compound

HRID 1485763Notes

Reaction equation

HRID 1485763 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][C:20]([F:23])([F:22])[CH2:19]2)=[O:16])[CH2:6][C@@H:5]1[CH3:24])(=[O:3])[CH3:2].CC1(C)OB([C:31]2[CH:32]=[N:33][N:34]([CH:36]3[CH2:39][N:38]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:37]3)[CH:35]=2)OC1(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>O>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:31]3[CH:32]=[N:33][N:34]([CH:36]4[CH2:37][N:38]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:39]4)[CH:35]=3)=[CH:11][CH:12]=2)[N:7]([C:15]([O:17][CH:18]2[CH2:21][C:20]([F:23])([F:22])[CH2:19]2)=[O:16])[CH2:6][C@@H:5]1[CH3:24])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 54576812tert-Butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylateHCID 118080494HCID 118080494, compound

Product 1

HCID 118080563HCID 118080563, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
90 °C

Procedure

A 100-mL round-bottom flask was purged with nitrogen and then charged with 3,3-difluorocyclobutyl (S)-4-acetyl-7-bromo-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate (300 mg, 0.70 mmol), tert-butyl 3-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylate (487 mg, 1.39 mmol), [1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II) dichloromethane complex (69 mg, 0.08 mmol), cesium carbonate (456 mg, 1.40 mmol), 1,4-dioxane (10 mL) and water (3 mL). The resulting mixture stirred overnight at 90° C. in an oil bath. After cooling to room temperature, the resulting mixture was diluted with water (10 mL) and extracted with ethyl acetate (3×15 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 8:1 ethyl acetate/petroleum ether) to afford 3,3-difluorocyclobutyl (S)-4-acetyl-7-(1-(1-(tert-butoxycarbonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate (300 mg, 79%) as a yellow oil. MS (ESI, pos. ion) m/z 546 [M+H]+.

Workup

  1. customA 100-mL round-bottom flask was purged with nitrogen
  2. temperatureAfter cooling to room temperature
  3. extractionextracted with ethyl acetate (3×15 mL)
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified via column chromatography on silica gel (eluting with 8:1 ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-0f4127c9ffe349ceb113e306a3e0d648
Source dataset
uspto-grants-2016_08
Patent number
US09422281B2

Reaction notes

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