N,N-Dimethylglycine → 1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethyl) phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60449

Reaktionsgleichung

Reaktionsgleichung von HRID 60449
Br[C:2]1[CH:24]=[N:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[C:3]=1C(C1C=CC(Cl)=CC=1)O.CN(C)CC(O)=O.C([O-])([O-])=O.[Cs+].[Cs+].[F:47][C:48]([F:57])([F:56])[C:49]1[CH:50]=[C:51]([OH:55])[CH:52]=[CH:53][CH:54]=1>O1CCOCC1.CC(=O)OCC.O.[Cu]I>[CH3:22][N:6]1[C:5]2[N:23]=[CH:24][C:2]([O:55][C:51]3[CH:52]=[CH:53][CH:54]=[C:49]([C:48]([F:47])([F:56])[F:57])[CH:50]=3)=[CH:3][C:4]=2[C:9](=[O:10])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)[C:7]1=[O:21]

Komponenten

9

Edukt 4

HCID 673N,N-DimethylglycineHCID 73763-(Trifluoromethyl)phenolHCID 10796Cesium carbonateHCID 1188755116-bromo-5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione2×

Produkt 1

HCID 1188755091-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethyl) phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneAusbeute 35 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a mixture of 6-bromo-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 20, step 4, 500 mg, 1.26 mmol), N,N-dimethylglycine (65 mg, 0.631 mmol), CuI (30 mg, 0.158 mmol) and Cs2CO3 (821 mg, 2.52 mmol) in dioxane (10 mL) was added 3-(trifluoromethyl)phenol (306 mg, 1.89 mmol). The reaction was heated at 100° C. for 18 h followed by heating at 120° C. for 8 h, cooled to RT then diluted with EA (50 mL) and water (20 mL). The organic layer was washed with water (2×20 mL) and brine (20 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (6:1) to give 1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethyl)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (210 mg, 35% yield) as a white solid. LCMS: [M++Na] 502 and TR=1.626 min.

Aufarbeitung

  1. temperatureby heating at 120° C. for 8 h
  2. temperaturecooled to RT
  3. washThe organic layer was washed with water (2×20 mL) and brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to a residue which
  6. customwas purified by chromatography
  7. washeluted with PE/EA (6:1)

Quellen und Nachweise

ORD-Eintrag
ord-2a8168c672f547ff85b7a57bd7e18cb2
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440972B2

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