Cesium carbonate → 5-Chloro-pyridine-2-carboxylic acid [6-(3-fluoromethyl-5-oxo-morpholin-3-yl)-pyridin-2-yl]-amide

HRID 538309Notes

Reaction equation

HRID 538309 reaction equation
C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:50]1[N:55]=[C:54]([C:56]2([CH2:63][F:64])[NH:61][C:60](=[O:62])[CH2:59][O:58][CH2:57]2)[CH:53]=[CH:52][CH:51]=1.[Cl:65][C:66]1[CH:67]=[CH:68][C:69]([C:72]([NH2:74])=[O:73])=[N:70][CH:71]=1>O1CCOCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.O>[F:64][CH2:63][C:56]1([C:54]2[N:55]=[C:50]([NH:74][C:72]([C:69]3[CH:68]=[CH:67][C:66]([Cl:65])=[CH:71][N:70]=3)=[O:73])[CH:51]=[CH:52][CH:53]=2)[CH2:57][O:58][CH2:59][C:60](=[O:62])[NH:61]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 218831585-Chloropyridine-2-carboxamideHCID 866680235-(6-Bromo-pyridin-2-yl)-5-fluoromethyl-morpholin-3-one

Product 1

HCID 866680245-Chloro-pyridine-2-carboxylic acid [6-(3-fluoromethyl-5-oxo-morpholin-3-yl)-pyridin-2-yl]-amide

Reagents, catalysts & solvents 3

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4,5-Bis(diphenyl phosphino)-9,9-dimethyl xanthene (0.04 g, 0.069 mmol), tris(dibenzylidene-acetone) di palladium(0) (0.032 g, 0.035 mmol) and cesium carbonate (0.678 g, 2.083 mmol) were taken in 1,4-dioxane and degassed with argon for 10 min. 5-(6-Bromo-pyridin-2-yl)-5-fluoromethyl-morpholin-3-one (0.2 g, 0.694 mmol) followed by 5-chloropicolinamide (0.119 g, 0.764 mmol) were added to the resultant reaction mixture and degassed with argon for further 5 min. Reaction mixture was then heated at 80° C. for 16 h and cooled to rt. Reaction contents were treated with water and product was extracted with ethyl acetate, washed with brine and dried over anhy. Na2SO4. The organic layer was concentrated under reduced pressure to obtain liquid which was triturated with n-pentane to furnish title compound as a off-white solid. Yield=0.24 g (crude). TLC (50% ethyl acetate in hexane) Rf=0.45; LCMS: RtH8=1.215, [M+1]=365.1 and 366.9; HPLC RtH9=4.367 min (53%).

Workup

  1. customdegassed with argon for 10 min
  2. additionwere added to the resultant
  3. customreaction mixture
  4. customdegassed with argon for further 5 min
  5. customReaction mixture
  6. temperaturecooled to rt
  7. customReaction contents
  8. extractionwas extracted with ethyl acetate
  9. washwashed with brine
  10. customdried over anhy
  11. concentrationThe organic layer was concentrated under reduced pressure
  12. customto obtain liquid which
  13. customwas triturated with n-pentane

Sources & evidence

ORD record
ord-444cdd52e76546678cea8838f56baba8
Source dataset
uspto-grants-2014_10
Patent number
US08865712B2

Reaction notes

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