Cesium carbonate → HCID 58044266, compound

HRID 1918845Notes

Reaction equation

HRID 1918845 reaction equation
[CH:1]1([N:4]2[CH:8]=[CH:7][C:6]([NH2:9])=[N:5]2)[CH2:3][CH2:2]1.BrC1[N:12]([CH3:19])[C:13](=O)[C:14]([Br:17])=NC=1.[C:20](=[O:23])([O-])[O-].[Cs+].[Cs+].[CH3:26][C:27]1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C(OCC)(=O)C.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Br:17][C:14]1[CH:26]=[C:27]([NH:9][C:6]2[CH:7]=[CH:8][N:4]([CH:1]3[CH2:3][CH2:2]3)[N:5]=2)[C:20](=[O:23])[N:12]([CH3:19])[CH:13]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 510000521-Cyclopropyl-1H-pyrazol-3-amineHCID 67016363HCID 67016363, compound

Product 1

HCID 58044266HCID 58044266, compoundYield 739.9%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A 250-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet was charged with 123b (444 mg, 3.61 mmol), 2,5-dibromo-1-methylpyrazin-6-one (1.06 g, 3.97 mmol), cesium carbonate (3.52 g, 10.8 mmol), and 1,4-dioxane (45 mL). After bubbling nitrogen through the resulting suspension for 30 min, Xantphos (177 mg, 0.306 mmol) and tris(dibenzylideneacetone)-dipalladium(0) (165 mg, 0.180 mmol) were added, and the reaction mixture was heated at reflux for 3 h. After this time, the mixture was cooled to room temperature and diluted with ethyl acetate (150 mL) and water (30 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×150 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was triturated with methanol (20 mL) to afford a 63% yield (700 mg) of 123c as an off-white solid: mp 161-163° C.; 1H NMR (300 MHz, DMSO-d6) d 8.42 (s, 1H), 8.00 (d, 1H, J=2.5 Hz), 7.57 (d, 1H, J=2.4 Hz), 7.38 (d, 1H, J=2.5 Hz), 6.05 (d, 1H, J=2.4 Hz), 3.61 (m, 1H), 3.49 (s, 1H), 0.95 (m, 4H); MS (ESI+) m/z 309.0 (M+H).

Workup

  1. customA 250-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet
  2. customAfter bubbling nitrogen through the resulting suspension for 30 min
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux for 3 h
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (3×150 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was triturated with methanol (20 mL)

Sources & evidence

ORD record
ord-23f81bca3114458c87694c7a58790b40
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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