Potassium Carbonate → 6-(2,4-Difluorophenoxy)-8-((r)-2-hydroxypropyl)-2-methylsulfanyl-8h-pyrido[2,3-d]pyrimidin-7-one

HRID 1393962Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1393962
[OH:1][C@H:2]([CH3:15])[CH2:3][NH:4][C:5]1[C:10]([CH:11]=O)=[CH:9][N:8]=[C:7]([S:13][CH3:14])[N:6]=1.C[O:17][C:18](=O)[CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=1[F:28].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[F:28][C:22]1[CH:23]=[C:24]([F:27])[CH:25]=[CH:26][C:21]=1[O:20][C:19]1[C:18](=[O:17])[N:4]([CH2:3][C@H:2]([OH:1])[CH3:15])[C:5]2[N:6]=[C:7]([S:13][CH3:14])[N:8]=[CH:9][C:10]=2[CH:11]=1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 23434554Methyl 2-(2,4-difluorophenoxy)acetateHCID 596814314-((r)-2-Hydroxy-propylamino)-2-methylsulfanyl-pyrimidine-5-carbaldehyde

Produkt 1

HCID 596814396-(2,4-Difluorophenoxy)-8-((r)-2-hydroxypropyl)-2-methylsulfanyl-8h-pyrido[2,3-d]pyrimidin-7-oneAusbeute 59,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a mixture of 4-((R)-2-hydroxy-propylamino)-2-methylsulfanyl-pyrimidine-5-carbaldehyde (17.7 g, 78 mmol) and (2,4-difluorophenoxy)acetic acid methyl ester (31.6 g, 156 mmol) in anhydrous dimethyl formamide (300 mL) was added potassium carbonate (30 g, 218 mmol). The reaction mixture was heated to 60° C. and after 18 hours, reaction mixture was cooled and DMF was distilled off. Residue suspended in water (300 mL) and extracted with dichloromethane, washed with brine and dried over magnesium sulfate. Filtered and concentrated under vacuum to give 29.5 g crude material which was chromatographed on silica gel column eluding with 1% methanol in dichloromethane to give 17.5 g 6-(2,4-difluorophenoxy)-8-((R)-2-hydroxypropyl)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one (mass spec M+1=274).

Aufarbeitung

  1. customreaction mixture
  2. temperaturewas cooled
  3. distillationDMF was distilled off
  4. extractionextracted with dichloromethane
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationFiltered
  8. concentrationconcentrated under vacuum
  9. customto give 29.5 g crude material which
  10. customwas chromatographed on silica gel column eluding with 1% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-f07c55c5c78741c39132bf01968516de
Quelldatensatz
uspto-grants-2008_03
Patentnummer
US07348331B2

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