Cesium carbonate → N-(2-[(2,3-Difluorobenzyl)thio]-6-{(1R)-1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy}pyrimidin-4-yl)morpholine-4-sulfonamide

HRID 1024935Notes

Reaction equation

HRID 1024935 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+].Cl[C:52]1[CH:57]=[C:56]([O:58][C@@H:59]([C@@H:61]2[CH2:65][O:64][C:63]([CH3:67])([CH3:66])[O:62]2)[CH3:60])[N:55]=[C:54]([S:68][CH2:69][C:70]2[CH:75]=[CH:74][CH:73]=[C:72]([F:76])[C:71]=2[F:77])[N:53]=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:77][C:71]1[C:72]([F:76])=[CH:73][CH:74]=[CH:75][C:70]=1[CH2:69][S:68][C:54]1[N:53]=[C:52]([NH:10][S:7]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)(=[O:9])=[O:8])[CH:57]=[C:56]([O:58][C@@H:59]([C@@H:61]2[CH2:65][O:64][C:63]([CH3:66])([CH3:67])[O:62]2)[CH3:60])[N:55]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 2767394-MorpholinesulfonamideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86619881HCID 86619881, compound

Product 1

HCID 53628371N-(2-[(2,3-Difluorobenzyl)thio]-6-{(1R)-1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy}pyrimidin-4-yl)morpholine-4-sulfonamide

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-morpholine sulfonamide (prepared according to patent WO 2004/011443) (0.15 g), tris(dibenzylideneacetone)dipalladium (0) (55 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (29 mg), cesium carbonate (0.30 g) and 4-chloro-2-[(2,3-difluorobenzyl)thio]-6-{(1R)-1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy}pyrimidine (the product of Example 47, step i) (0.25 g) in dioxane (5 ml). The crude material was purified by column chromatography using EtOAc/isohexane (1:9 to 2.5:7.5 gradient) as eluent to give the subtitle compound as an off-white foam. Yield: 0.20 g.

Workup

  1. customThe subtitle compound was prepared
  2. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-e6fcbe6358b34e2d9266ff4620f7e853
Source dataset
uspto-grants-2014_05
Patent number
US08722883B2

Reaction notes

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