2-Bromopyridine → HCID 25027937, compound

HRID 1864474Notes

Reaction equation

HRID 1864474 reaction equation
CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:49]1([S:55]([N:58]2[CH2:62][C@@H:61]([C:63]([N:65]3[CH2:70][CH2:69][N:68]([C:71]4[CH:76]=[C:75]([CH3:77])[CH:74]=[CH:73][C:72]=4[CH3:78])[CH2:67][CH2:66]3)=[O:64])[NH:60][C:59]2=[O:79])(=[O:57])=[O:56])[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1.Br[C:81]1[CH:86]=[CH:85][CH:84]=[CH:83][N:82]=1.C([O-])(O)=O.[Na+]>O1CCOCC1.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]>[C:49]1([S:55]([N:58]2[CH2:62][C@@H:61]([C:63]([N:65]3[CH2:66][CH2:67][N:68]([C:71]4[CH:76]=[C:75]([CH3:77])[CH:74]=[CH:73][C:72]=4[CH3:78])[CH2:69][CH2:70]3)=[O:64])[N:60]([C:81]3[CH:86]=[CH:85][CH:84]=[CH:83][N:82]=3)[C:59]2=[O:79])(=[O:57])=[O:56])[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1

Participants

8

Reactant 5

HCID 79732-BromopyridineHCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 67141101HCID 67141101, compound

Product 1

HCID 25027937HCID 25027937, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

Under argon an oven-dried flask was charged with tris(dibenzylideneacetone)dipalladium (2.5 mg), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (4.7 mg), cesium carbonate (41.2 mg) and dioxane (0.75 mL). The mixture was stirred for 30 min, before a mixture of (S)-1-benzenesulfonyl-4-[4-(2,5-dimethyl-phenyl)-piperazine-1-carbonyl]-imidazolidin-2-one (example 66, step 3) (40 mg) and 2-bromopyridine (17.1 mg) in dioxane (0.75 mL) was added. The reaction mixture was heated to 100° C. for 4 hours and was stirred at room temperature over night. The mixture was cooled to room temperature, an aqueous solution of NaHCO3 was added, the phases were separated, and the inorganic one was extracted with ethyl acetate (×3). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. Purification by chromatography (SiO2, CH2Cl2/ethyl acetate 4:1 to ethyl acetate) gave (S)-1-benzenesulfonyl-4-[4-(2,5-dimethyl-phenyl)-piperazine-1-carbonyl]-3-pyridin-2-yl-imidazolidin-2-one as a light yellow solid, MS: 519.8 ([M+H]+).

Workup

  1. additionwas added
  2. temperatureThe mixture was cooled to room temperature
  3. customthe phases were separated
  4. extractionthe inorganic one was extracted with ethyl acetate (×3)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customPurification by chromatography (SiO2, CH2Cl2/ethyl acetate 4:1 to ethyl acetate)

Sources & evidence

ORD record
ord-624ddbdb7b094e348bceaa744cd7da58
Source dataset
uspto-grants-2009_12
Patent number
US07625902B2

Reaction notes

Loading…