Cesium carbonate → N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-methyl-2-(triphenylmethoxy)ethoxy]-4-pyrimidinyl]-4-pyridinesulfonamide

HRID 1958911Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1958911
[N:1]1[CH:6]=[CH:5][C:4]([S:7]([NH2:10])(=[O:9])=[O:8])=[CH:3][CH: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]([CH3:81])[CH2:60][O:61][C:62]([C:75]2[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=2)([C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)[C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[N:55]=[C:54]([S:82][CH2:83][C:84]2[CH:89]=[CH:88][CH:87]=[C:86]([F:90])[C:85]=2[F:91])[N:53]=1>O1CCOCC1.C(Cl)Cl.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:91][C:85]1[C:86]([F:90])=[CH:87][CH:88]=[CH:89][C:84]=1[CH2:83][S:82][C:54]1[N:53]=[C:52]([NH:10][S:7]([C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)(=[O:9])=[O:8])[CH:57]=[C:56]([O:58][C@H:59]([CH3:81])[CH2:60][O:61][C:62]([C:63]2[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=2)([C:75]2[CH:76]=[CH:77][CH:78]=[CH:79][CH:80]=2)[C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)[N:55]=1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 12383449Pyridine-4-sulfonamide2×HCID 536283454-chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-methyl-2-(triphenylmethoxy)ethoxy]-pyrimidine2×

Produkt 1

HCID 53628344N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-methyl-2-(triphenylmethoxy)ethoxy]-4-pyrimidinyl]-4-pyridinesulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 4-pyridinesulfonamide (the product from step i) (0.21 g), tris(dibenzylideneacetone)dipalladium (0) (50 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (50 mg), cesium carbonate (0.66 g) and 4-chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-methyl-2-(triphenylmethoxy)ethoxy]-pyrimidine (the product from step iii) (0.40 g) in dioxane (20 mL) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 3 h. The reaction mixture was diluted with DCM, filtered through arbocel and the filtrate evaporated. The residue was purified by reverse phase HPLC using a TFA (0.2%)/MeCN system to give the title compound as a yellow solid. Yield: 0.21 g.

Aufarbeitung

  1. temperaturewas heated
  2. temperature300 W, open vessel with cooling for 3 h
  3. filtrationfiltered through arbocel
  4. customthe filtrate evaporated
  5. customThe residue was purified by reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-15baf0acaf924d5ba30466f3b56068ad
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08410123B2

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