Cesium carbonate → N-[2-[(2,3-Difluorobenzyl)thio]-6-(2-hydroxyethoxy)pyrimidin-4-yl]methanesulfonamide

HRID 1024987Notes

Reaction equation

HRID 1024987 reaction equation
[CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:47]1[N:52]=[C:51]([S:53][CH2:54][C:55]2[CH:60]=[CH:59][CH:58]=[C:57]([F:61])[C:56]=2[F:62])[N:50]=[C:49]([O:63][CH2:64][CH2:65][OH:66])[CH:48]=1>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]>[F:62][C:56]1[C:57]([F:61])=[CH:58][CH:59]=[CH:60][C:55]=1[CH2:54][S:53][C:51]1[N:52]=[C:47]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])[CH:48]=[C:49]([O:63][CH2:64][CH2:65][OH:66])[N:50]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 72879MethanesulfonamideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866198902-({6-Chloro-2-[(2,3-difluorobenzyl)thio]pyrimidin-4-yl)oxy}ethanol

Product 1

HCID 59558835N-[2-[(2,3-Difluorobenzyl)thio]-6-(2-hydroxyethoxy)pyrimidin-4-yl]methanesulfonamide

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of methanesulfonamide (0.228 g), tris(dibenzylideneacetone)dipalladium (0) (50 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (50 mg), cesium carbonate (0.585 g) and 2-({6-chloro-2-[(2,3-difluorobenzyl)thio]pyrimidin-4-yl)oxy}ethanol ((the product step i), 0.400 g) in dioxane (20 ml) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 30 mins. The reaction mixture was then reduced in vacuo and the residue separated between DCM (150 ml) and H2O (100 ml). The organics were separated and the aqueous layer was re-extracted with DCM (2×150 ml). Organics were combined, dried (MgSO4) and reduced in vacuo and the resulting residue was purified by prep HPLC to give the title compound as a white solid. Yield: 102 mg

Workup

  1. temperaturewas heated
  2. temperature300 W, open vessel with cooling for 30 mins
  3. customthe residue separated between DCM (150 ml) and H2O (100 ml)
  4. customThe organics were separated
  5. extractionthe aqueous layer was re-extracted with DCM (2×150 ml)
  6. dry with materialdried (MgSO4)
  7. customthe resulting residue was purified by prep HPLC

Sources & evidence

ORD record
ord-157c52267c4f4a40a653a579ce5308ce
Source dataset
uspto-grants-2014_05
Patent number
US08722883B2

Reaction notes

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