4-Amino-2,6-dimethylpyridine → 6-(3,5-Dimethoxy-phenyl)-2-(2,6-dimethyl-pyridin-4-ylamino)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-one

HRID 1793882

Reaktionsgleichung

Reaktionsgleichung von HRID 1793882
[NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([CH3:9])[CH:3]=1.C([Li])CCC.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([C:25]2[C:37](=[O:38])[N:36]([CH2:39][CH3:40])[C:28]3[N:29]=[C:30](S(C)=O)[N:31]=[CH:32][C:27]=3[CH:26]=2)[CH:20]=[C:21]([O:23][CH3:24])[CH:22]=1.C(OCC)(=O)C.O>C1COCC1.CO.C(Cl)(Cl)Cl>[CH3:24][O:23][C:21]1[CH:20]=[C:19]([C:25]2[C:37](=[O:38])[N:36]([CH2:39][CH3:40])[C:28]3[N:29]=[C:30]([NH:1][C:2]4[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([CH3:9])[CH:3]=4)[N:31]=[CH:32][C:27]=3[CH:26]=2)[CH:18]=[C:17]([O:16][CH3:15])[CH:22]=1

Komponenten

7

Edukt 4

HCID 770474-Amino-2,6-dimethylpyridineHCID 222201672-methylsulfinyl-6-(3,5-dimethoxy-phenyl)8-ethyl-8H-pyrido[2,3-d]pyrimidine-7-oneHCID 22728543Water ethylacetateHCID 178418339Butyllithium

Produkt 1

HCID 222201926-(3,5-Dimethoxy-phenyl)-2-(2,6-dimethyl-pyridin-4-ylamino)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-oneAusbeute 28 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 21584188Chloroform methanolLösungsmittel

Reaktionsbedingungen

Temperatur
-10 °C

Versuchsvorschrift

To a −78° C. solution of 3.9 g (32.1 mmol) of 4-amino-2,6-dimethylpyridine in 120 mL of THF was added dropwise 17.5 mL (30.5 mmol) of 1.6 M n-butyllithium in hexanes. The reaction solution was stirred for 15 minutes at which time 3.0 g (8.0 mmol) of the product of Example 7, 6-(3,5-dimethoxy-phenyl)-8-ethyl-2-methanesulfinyl-8H-pyrido[2,3-d]pyrimidin-7-one, was added in small portions as a solid. The reaction mixture was allowed to warm slowly to −10° C. then remain at −10° C. overnight. The reaction. mixture was poured into ethyl acetate/water/5 mL 6N HCl. The mixture was shaken and separated. The organic phase was washed with a saturated solution of sodium bicarbonate, twice with water, and brine, then dried over magnesium sulfate, filtered, and concentrated to a solid residue. The residue was triturated under ethyl acetate/dichloromethane. The resulting material was further purified by column chromatography eluting with 5:50:50 methanol/ethyl acetate/dichloromethane to give an orange crystalline material. This material was dissolved in 150 mL of hot 1:9 methanol/chloroform and filtered. The addition of 60 mL of hexane results in the precipitation of 0.99 g (28%) of the title compound as a pale yellow solid.

Aufarbeitung

  1. additionwas added in small portions as a solid
  2. customThe reaction
  3. customseparated
  4. washThe organic phase was washed with a saturated solution of sodium bicarbonate, twice with water, and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to a solid residue
  8. customThe residue was triturated under ethyl acetate/dichloromethane
  9. customThe resulting material was further purified by column chromatography
  10. washeluting with 5:50:50 methanol/ethyl acetate/dichloromethane
  11. customto give an orange crystalline material
  12. filtrationfiltered
  13. additionThe addition of 60 mL of hexane

Quellen und Nachweise

ORD-Eintrag
ord-99687acc8f5c45708267614a9736c761
Quelldatensatz
uspto-grants-2006_04
Patentnummer
US07022711B2

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