Cesium carbonate → N-{2-[(2,3-difluorobenzyl)thio]-6-[(1R)-1-methyl-2-(trityloxy)ethoxy]pyrimidin-4-yl}-4-methylpiperazine-1-sulfonamide

HRID 1024951Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1024951
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([S:8]([NH2:11])(=[O:10])=[O:9])[CH2:4][CH2:3]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+].Cl[C:53]1[CH:58]=[C:57]([O:59][C@H:60]([CH3:82])[CH2:61][O:62][C:63]([C:76]2[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=2)([C:70]2[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=2)[C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)[N:56]=[C:55]([S:83][CH2:84][C:85]2[CH:90]=[CH:89][CH:88]=[C:87]([F:91])[C:86]=2[F:92])[N:54]=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:92][C:86]1[C:87]([F:91])=[CH:88][CH:89]=[CH:90][C:85]=1[CH2:84][S:83][C:55]1[N:54]=[C:53]([NH:11][S:8]([N:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)(=[O:10])=[O:9])[CH:58]=[C:57]([O:59][C@H:60]([CH3:82])[CH2:61][O:62][C:63]([C:76]2[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=2)([C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)[C:70]2[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=2)[N:56]=1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 143260054-Methylpiperazine-1-sulfonamide2×HCID 536283454-chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-methyl-2-(triphenylmethoxy)ethoxy]-pyrimidine

Produkt 1

HCID 53628375N-{2-[(2,3-difluorobenzyl)thio]-6-[(1R)-1-methyl-2-(trityloxy)ethoxy]pyrimidin-4-yl}-4-methylpiperazine-1-sulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 4-Methylpiperazine-1-sulfonamide (the product from step i) (0.64 g), tris(dibenzylideneacetone)dipalladium (0) (50 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (50 mg), cesium carbonate (0.55 g) and 4-chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-[(1R)-1-methyl-2-(triphenylmethoxy)ethoxy]-pyrimidine ((the product of example 13 step iii), 0.50 g) in dioxane (40 mL) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 1 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 subtitle compound as a yellow solid. Yield: 0.22 g.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-2c1418836e7b423eb564cf720c5f010b
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08722883B2

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