Potassium Carbonate → 7-((5-fluoropyridin-3-yl)methyl)-1-(3-hydroxypropyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione

HRID 2200723Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2200723
[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[C:13](=[O:14])[C:12]2[NH:11][C:10]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:26])([F:25])[F:24])[CH:17]=3)=[N:9][C:8]=2[N:7]([CH3:27])[C:6]1=[O:28].Cl[CH2:30][C:31]1[CH:32]=[N:33][CH:34]=[C:35]([F:37])[CH:36]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[F:37][C:35]1[CH:36]=[C:31]([CH2:30][N:11]2[C:12]3[C:13](=[O:14])[N:5]([CH2:4][CH2:3][CH2:2][OH:1])[C:6](=[O:28])[N:7]([CH3:27])[C:8]=3[N:9]=[C:10]2[O:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:25])([F:26])[F:24])[CH:17]=2)[CH:32]=[N:33][CH:34]=1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 216984253-(Chloromethyl)-5-fluoropyridineHCID 904027281-(3-hydroxypropyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione2×

Produkt 1

HCID 904026457-((5-fluoropyridin-3-yl)methyl)-1-(3-hydroxypropyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dioneAusbeute 46 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 67553Tetrabutylammonium IodideKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of 1-(3-hydroxypropyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (60 mg, 0.15 mmol, intermediate 15) in DMF (5 mL) was added 3-(chloromethyl)-5-fluoropyridine (80 mg, 0.55 mmol), potassium carbonate (0.55 g, 0.6 mmol), and TBAI (2 mg, 0.02 mmol). The reaction was heated at 60° C. for 2 h. The mixture was cooled and partitioned between ethyl acetate and water. The organic phase was dried over sodium sulfate, and concentrated. The residue was purified by preparative HPLC to give 7-((5-fluoropyridin-3-yl)methyl)-1-(3-hydroxypropyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (35 mg, 46% yield) as white solid. LCMS retention time 2.577 min; LCMS MH+ 510.

Aufarbeitung

  1. temperatureThe mixture was cooled
  2. custompartitioned between ethyl acetate and water
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-2981850ecac644a6ab06ce36c6fbffc9
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09359359B2

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