Phenolate → 1-(6-chloropyridin-3-yl)-9-methyl-2-(3,4,5-trifluorophenoxy)-1H-purin-6(9H)-one

HRID 408842Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 408842
[CH3:1]C([O-])(C)C.[K+].[F:7][C:8]1[CH:9]=[C:10]([OH:16])[CH:11]=[C:12]([F:15])[C:13]=1[F:14].[O-]C1C=CC=CC=1.Cl[C:25]1[N:26]([C:35]2[CH:36]=[N:37][C:38]([Cl:41])=[CH:39][CH:40]=2)[C:27](=[O:34])[C:28]2[N:29]=[CH:30][NH:31][C:32]=2[N:33]=1>C(O)(C)C.CC(N(C)C)=O>[Cl:41][C:38]1[N:37]=[CH:36][C:35]([N:26]2[C:27](=[O:34])[C:28]3[N:29]=[CH:30][N:31]([CH3:1])[C:32]=3[N:33]=[C:25]2[O:16][C:10]2[CH:9]=[C:8]([F:7])[C:13]([F:14])=[C:12]([F:15])[CH:11]=2)=[CH:40][CH:39]=1

Komponenten

7

Edukt 4

HCID 119047PhenolateHCID 27779433,4,5-TrifluorophenolHCID 23665647Potassium tert-butoxideHCID 178515262HCID 178515262, Verbindung

Produkt 1

HCID 249578951-(6-chloropyridin-3-yl)-9-methyl-2-(3,4,5-trifluorophenoxy)-1H-purin-6(9H)-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3776IsopropanolLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

1.0 M KOtBu in isopropanol (2 mL) is added to the solution of 3,4,5-trifluorophenol (0.29 g, 1.86 mmol) and stirred for 20 minutes at RT. To the resulting phenoxide solution is added a solution of 2-chloro-1-(6-chloropyridin-3-yl)-1,9-dihydro-6H-purin-6-one (0.5 g, 1.69 mmol) in dimethylacetamide (3 mL) and the resulting mixture is stirred overnight at 50° C. The resulting reaction mixture is cooled, quenched with saturated NH4Cl solution, extracted with DCM (2×50 mL) and dried (Na2SO4). The organic layer is filtered and concentrated under vacuum to afford the crude product as a light brown solid. The crude product is further purified by flash column chromatography using 5% MeOH/CH2Cl2 to afford the title compound as white solid. 1H NMR (300 MHz, CDCl3) δ 8.41 (s, 1H), 7.55-7.81 (m, 2H), 7.4 (brs, 1H), 6.71-7.02 (m, 2H), 3.85 (s, 3H). MS (M+1): 408.04; RT=1.48 min. The IC50 determined as described in Example 6 is 100 nanomolar or less.

Aufarbeitung

  1. stirringthe resulting mixture is stirred overnight at 50° C
  2. customThe resulting reaction mixture
  3. temperatureis cooled
  4. customquenched with saturated NH4Cl solution
  5. extractionextracted with DCM (2×50 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationThe organic layer is filtered
  8. concentrationconcentrated under vacuum
  9. customto afford the crude product as a light brown solid
  10. customThe crude product is further purified by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-f3f57153e34d4ee4b186f66cadeca7c6
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759361B2

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