Cesium carbonate → 3-{5-Methyl-2-[4-(2-pyrrolidin-1-yl-ethoxy)-phenylamino]-pyrimidin-4-ylamino}-benzenesulfonamide

HRID 1095034

Reaktionsgleichung

Reaktionsgleichung von HRID 1095034
[CH3:1][C:2]1[C:3]([NH2:23])=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:11][CH:10]=2)=[N:6][CH:7]=1.Br[C:25]1[CH:26]=[C:27]([S:31]([NH2:34])(=[O:33])=[O:32])[CH:28]=[CH:29][CH:30]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CN(C=O)C.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]>[CH3:1][C:2]1[C:3]([NH:23][C:25]2[CH:26]=[C:27]([S:31]([NH2:34])(=[O:33])=[O:32])[CH:28]=[CH:29][CH:30]=2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([O:15][CH2:16][CH2:17][N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:13][CH:14]=2)=[N:6][CH:7]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27347653-Bromobenzene-1-sulfonamideHCID 576750855-Methyl-N2-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)pyrimidine-2,4-diamine

Produkt 1

HCID 448160803-{5-Methyl-2-[4-(2-pyrrolidin-1-yl-ethoxy)-phenylamino]-pyrimidin-4-ylamino}-benzenesulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 217120691,4-dioxane N,N-dimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of intermediate 38 (0.10 g, 0.32 mmol), 3-bromo-benzenesulfonamide (0.10 g, 0.42 mmol), Pd2(dba)3 (20 mg, 0.022 mmol), Xantphos (25 mg, 0.043 mmol) and cesium carbonate (0.20 g, 0.61 mmol) in dioxane/DMF (3/1, 4 mL) was sealed in a microwave reaction tube and irradiated with microwave at 170° C. for 25 min. After cooling to room temperature, the cap was removed and the resulting mixture filtered and the filtered solid washed with DCM. The filtrate was concentrated and the residue purified by HPLC. The corrected fractions were combined and poured into saturated NaHCO3 solution (30 mL). The aqueous layer was extracted with EtOAc (2×30 mL) and the combined organic layers washed with brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated and solid triturated in a mixture of EtOAc/hexanes (1/10, 33 mL). After filtration, the title compound was obtained as a white solid (11 mg, 7%).

Aufarbeitung

  1. customwas sealed in a microwave reaction tube
  2. customirradiated with microwave at 170° C. for 25 min
  3. customthe cap was removed
  4. filtrationthe resulting mixture filtered
  5. washthe filtered solid washed with DCM
  6. concentrationThe filtrate was concentrated
  7. customthe residue purified by HPLC
  8. additionpoured into saturated NaHCO3 solution (30 mL)
  9. extractionThe aqueous layer was extracted with EtOAc (2×30 mL)
  10. washthe combined organic layers washed with brine
  11. dry with materialdried over anhydrous Na2SO4
  12. filtrationfiltered
  13. concentrationThe filtrate was concentrated
  14. customsolid triturated in a mixture of EtOAc/hexanes (1/10, 33 mL)
  15. filtrationAfter filtration

Quellen und Nachweise

ORD-Eintrag
ord-b107043f692649edb4867387013aa6ce
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08133900B2

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