Potassium Carbonate → 5-chloro-3-(5-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2-methylphenyl)-2-methyl-6-((2-methyloxazol-4-yl)methoxy)pyrimidin-4(3H)-one

HRID 2172611Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2172611
[Cl:1][C:2]1[C:3](=[O:27])[N:4]([C:10]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]([OH:25])([CH3:24])[CH3:23])[N:17]=3)[CH:13]=[CH:12][C:11]=2[CH3:26])[C:5]([CH3:9])=[N:6][C:7]=1[OH:8].Cl[CH2:29][C:30]1[N:31]=[C:32]([CH3:35])[O:33][CH:34]=1.C(=O)([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1>CN(C)C=O>[Cl:1][C:2]1[C:3](=[O:27])[N:4]([C:10]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]([OH:25])([CH3:23])[CH3:24])[N:17]=3)[CH:13]=[CH:12][C:11]=2[CH3:26])[C:5]([CH3:9])=[N:6][C:7]=1[O:8][CH2:29][C:30]1[N:31]=[C:32]([CH3:35])[O:33][CH:34]=1

Komponenten

6

Edukt 4

HCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 216983214-(Chloromethyl)-2-methyl-1,3-oxazoleHCID 1363878065-Chloro-6-hydroxy-3-{5-[2-(1-hydroxy-1-methyl-ethyl)-pyrimidin-4-yl]-2-methyl-phenyl}-2-methyl-3H-pyrimidin-4-one

Produkt 1

HCID 715823385-chloro-3-(5-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2-methylphenyl)-2-methyl-6-((2-methyloxazol-4-yl)methoxy)pyrimidin-4(3H)-oneAusbeute 25 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of Intermediate 1 (509 mg, 1.32 mmol) in N,N-dimethylformamide (5 mL) was added 4-chloromethyl-2-methyl-oxazole from Step A (173 mg, 1.32 mmol), potassium carbonate (273 mg, 1.98 mmol) and 18-crown-6 (40 mg). The slurry was heated at 60° C. for eighteen hours. The reaction was allowed to cool to room temperature and then partitioned between ethyl acetate and water. The organic layer was washed with water and brine and dried over magnesium sulfate. The slurry was filtered and concentrated in vacuo. The crude material was purified using normal phase chromatography (ethyl acetate/heptane) to provide the title compound as a colorless oil. (160 mg, 25% yield). MS (M+H): 482; 1H NMR (400 MHz, chloroform-d) δ ppm, 1.64 (s, 6H), 2.17 (s, 3H), 2.20 (s, 3H), 2.50 (s, 3H), 5.40-5.48 (m, 2H), 7.54-7.58 (m, 2H), 7.66 (s, 1H), 7.93 (s, 1H), 8.13 (d, J=8.21 Hz, 1H), 8.77 (d, J=5.08, 1H).

Aufarbeitung

  1. temperatureto cool to room temperature
  2. custompartitioned between ethyl acetate and water
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe slurry was filtered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified

Quellen und Nachweise

ORD-Eintrag
ord-eec20624d96f48858e0034a06ab06602
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09056110B2

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