Potassium Carbonate → Methyl 2-[1-[[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-pyrimidin-1-yl]methyl]cyclopropyl]acetate

HRID 2194767Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2194767
[CH:1]([C:4]1[C:9](=[O:10])[NH:8][C:7](=[O:11])[NH:6][C:5]=1[C:12]([C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([CH3:22])[CH:21]=1)[C:17]#[N:18])=[O:13])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[I-].[Li+].[CH3:31][O:32][C:33](=[O:44])[CH2:34][C:35]1([CH2:38]OS(C)(=O)=O)[CH2:37][CH2:36]1>CN(C=O)C>[CH3:31][O:32][C:33](=[O:44])[CH2:34][C:35]1([CH2:38][N:6]2[C:5]([C:12](=[O:13])[C:14]3[CH:21]=[C:20]([CH3:22])[CH:19]=[C:16]([C:17]#[N:18])[CH:15]=3)=[C:4]([CH:1]([CH3:3])[CH3:2])[C:9](=[O:10])[NH:8][C:7]2=[O:11])[CH2:37][CH2:36]1

Komponenten

6

Edukt 4

HCID 11430Potassium CarbonateHCID 66321Lithium iodideHCID 468803773-(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrileHCID 58203553Methyl 2-(1-[(methanesulfonyloxy)-methyl]cyclopropyl)acetate

Produkt 1

HCID 25214958Methyl 2-[1-[[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-pyrimidin-1-yl]methyl]cyclopropyl]acetateAusbeute 13,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

To a mixture of 3-(5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrile (962 mg, 4.16 mmol), anhydrous powdered potassium carbonate (574 mg, 4.16 mmol), and lithium iodide (557 mg, 4.16 mmol), was added DMF (18 mL) at room temperature. After stirring for 30 min, crude (1-methanesulfonyloxymethyl-cyclopropyl)-acetic acid methyl ester (962 mg) in DMF (2 mL) was added. The mixture was then heated in an oil bath (70-80° C.) and stirred for ca. 19 hr. After cooling to room temperature, the mixture was evaporated in vacuo. The residue was dissolved in methanol-dichloromethane (5:95) and filtered through a celite pad. The filtrate was evaporated and the residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane (1:2)) to give 230 mg (13%) of {1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-acetic acid methyl ester (82) as a white syrup. 1H-NMR (200 MHz, CDCl3) δ 0.36-0.65 (4H, m), 1.12 (3H, d, J=7.0 Hz), 1.23 (3H, d, J=7.0 Hz), 2.17-2.32 (2H, m), 2.44-2.52 (4H, m), 3.58 (1H, d, J=15.2 Hz), 3.69 (3H, s), 3.76 (1H, d, J=15.2 Hz), 7.79 (1H, s), 7.95 (1H, s), 8.06 (1H, s), 9.36 (1H, s); m/z (EI) 423 (M+).

Aufarbeitung

  1. stirringstirred for ca. 19 hr
  2. temperatureAfter cooling to room temperature
  3. customthe mixture was evaporated in vacuo
  4. dissolutionThe residue was dissolved in methanol-dichloromethane (5:95)
  5. filtrationfiltered through a celite pad
  6. customThe filtrate was evaporated
  7. customthe residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane (1:2))

Quellen und Nachweise

ORD-Eintrag
ord-8bbc0f36990b400f8de8ff5c38cdf807
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08334295B2

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