Cesium carbonate → 2-[[2-[[(2,3-difluorophenyl)methyl]thio]-6-[[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino]-4-pyrimidinyl]oxy]-(2R)-propanoic acid ethyl ester

HRID 1024883Notes

Reaction equation

HRID 1024883 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([S:7]([NH2:10])(=[O:9])=[O:8])[N:4]=[CH:3]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]([C:5]2[N:4]=[CH:3][N:2]([CH3:1])[CH:6]=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 27368851-methyl-1H-imidazole-4-sulfonamideHCID 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 536283532-[[2-[[(2,3-difluorophenyl)methyl]thio]-6-[[(1-methyl-1H-imidazol-4-yl)sulfonyl]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 1-methyl-1H-imidazole-4-sulfonamide (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: 0.28 g

Workup

  1. customThe subtitle compound was prepared
  2. customPurification

Sources & evidence

ORD record
ord-982c9e96347d48d28ba356fb7c2de2d4
Source dataset
uspto-grants-2014_05
Patent number
US08722883B2

Reaction notes

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