Cesium carbonate → 2-[[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(4-morpholinylsulfonyl)amino]-4-pyrimidinyl]oxy]-(2R)-propanoic acid ethyl ester

HRID 1024877Notes

Reaction equation

HRID 1024877 reaction equation
[N:1]1([S:7]([NH2:10])(=[O:9])=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.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+].[CH2:51]([O:53][C:54](=[O:75])[C@H:55]([O:57][C:58]1[CH:63]=[C:62](Cl)[N:61]=[C:60]([S:65][CH2:66][C:67]2[CH:72]=[CH:71][CH:70]=[C:69]([F:73])[C:68]=2[F:74])[N:59]=1)[CH3:56])[CH3:52]>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>[CH2:51]([O:53][C:54](=[O:75])[C@H:55]([O:57][C:58]1[CH:63]=[C:62]([NH:10][S:7]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)(=[O:9])=[O:8])[N:61]=[C:60]([S:65][CH2:66][C:67]2[CH:72]=[CH:71][CH:70]=[C:69]([F:73])[C:68]=2[F:74])[N:59]=1)[CH3:56])[CH3:52]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 2767394-MorpholinesulfonamideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866198702-[[6-chloro-2-[[(2,3-difluorophenyl)methyl]thio]-4-pyrimidinyl]oxy](2R)-propanoic acid ethyl ester

Product 1

HCID 536283512-[[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(4-morpholinylsulfonyl)amino]-4-pyrimidinyl]oxy]-(2R)-propanoic acid ethyl ester

Reagents, catalysts & solvents 2

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

Procedure

The subtitle compound was prepared according to the procedure outlined in example 1 step iv) using a mixture of 4-morpholinesulfonamide (prepared according to patent WO 2004/011443, 0.19 g), tris(dibenzylideneacetone)dipalladium (0) (71 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (52 mg), cesium carbonate (0.38 g), 2-[[6-chloro-2-[[(2,3-difluorophenyl)methyl]thio]-4-pyrimidinyl]oxy](2R)-propanoic acid ethyl ester (the product of Example 23 step i) (0.30 g) and dioxane (10 mL). Purification was by column chromatography on silica gel using EtOAc/isohexane (1:1) as eluent to give the subtitle compound as an oil. Yield: 0.34 g

Workup

  1. customThe subtitle compound was prepared
  2. customPurification

Sources & evidence

ORD record
ord-1479182345b24b42807a34878be31bf8
Source dataset
uspto-grants-2014_05
Patent number
US08722883B2

Reaction notes

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