Cesium carbonate → HCID 178479983, compound

HRID 1918869Notes

Reaction equation

HRID 1918869 reaction equation
[NH2:1][C:2]1[N:6](C(OC(C)(C)C)=O)[N:5]=[C:4]([CH:14]2[CH2:16][CH2:15]2)[CH:3]=1.Br[C:18]1[C:19](=[O:26])[N:20]([CH3:25])[CH:21]=[C:22]([Br:24])[CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(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>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:24][C:22]1[CH:23]=[C:18]([NH:1][C:2]2[NH:6][N:5]=[C:4]([CH:14]3[CH2:15][CH2:16]3)[CH:3]=2)[C:19](=[O:26])[N:20]([CH3:25])[CH:21]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 11356513tert-butyl 5-amino-3-cyclopropyl-1H-pyrazole-1-carboxylate

Product 1

HCID 178479983HCID 178479983, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (15 mL), 136c (455 mg, 1.95 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (0.40 g, 1.5 mmol) and cesium carbonate (1.22 g, 3.75 mmol). After bubbling nitrogen through the resulting mixture for 30 minutes, XantPhos (87 mg, 0.15 mmol) and tris(dibenzylideneacetone)dipalladium(0) (70 mg, 0.075 mmol) were added, and the reaction mixture was heated at reflux for 15 h. After this time the reaction was cooled to room temperature, partitioned between ethyl acetate (30 mL) and water (30 mL) and filtered. The aqueous layer was separated and extracted with ethyl acetate 2×50 mL). The organic layers were combined, washed with brine (50 mL) and dried over Na2SO4. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified on flash column eluting with 50:1 CH2Cl2/MeOH to afford 136d as a yellow solid (320 mg, 50%). LCMS: (M+H)+ 309. 1H NMR (500 MHz, DMSO) δ 11.85 (s, 1H), 8.23 (s, 1H), 8.02 (d, J=2.5, 1H), 7.35 (d, J=2.5, 1H), 5.77 (d, J=2, 1H), 3.46 (s, 3H), 1.83 (m, 1H), 0.90 (m, 2H), 0.64 (m, 2H)

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. customAfter bubbling nitrogen through the resulting mixture for 30 minutes
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 15 h
  6. custompartitioned between ethyl acetate (30 mL) and water (30 mL)
  7. filtrationfiltered
  8. customThe aqueous layer was separated
  9. extractionextracted with ethyl acetate 2×50 mL)
  10. washwashed with brine (50 mL)
  11. dry with materialdried over Na2SO4
  12. customThe drying agent was removed by filtration
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customThe residue was purified on flash column
  15. washeluting with 50:1 CH2Cl2/MeOH

Sources & evidence

ORD record
ord-1afbff5148c04d4092143eb5ff79aeb4
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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