Reaktion #528154

Reaktionsgleichung

2,4-diamino-6-ethyl-5-(3-amino-4-chlorophenyl)pyrimidine

undecanoyl chloride

→

2,4-diamino-6-ethyl-5-(4-chloro-3-decylcarbonylaminophenyl)pyrimidine

Lösungsmittel

water

pyridine

tetrahydrofuran

water

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooled in an ice bath
2. 2
   workup.ADDITIONTo this was added dropwise during a 10 minute period
3. 3
   TemperaturThe reaction mixture was maintained below about 10° C. throughout the addition
4. 4
   workup.ADDITIONUpon completion of addition
5. 5
   ExtraktionThe mixture was then extracted with two 200 mL portions of ethyl acetate
6. 6
   WaschenThe combined extracts were washed with 150 mL of aqueous 10% lithium chloride
7. 7
   TrocknenThe organic layer was dried with magnesium sulfate
8. 8
   Filtrationfiltered
9. 9
   EinengenThe filtrate was concentrated under reduced pressure to a residue
10. 10
    SonstigeIn an effort to remove any excess pyridine
11. 11
    Einengenthe solution was concentrated under reduced pressure to a residue
12. 12
    WaschenElution
13. 13
    Einengenconcentrated under reduced pressure

Vorschrift

Under a nitrogen atmosphere, a solution of 2.5 grams (0.001 mole) of 2,4-diamino-6-ethyl-5-(3-amino-4-chlorophenyl)pyrimidine (prepared in Step B of this Example) in 75 mL of pyridine and 25 mL of tetrahydrofuran was stirred and cooled in an ice bath. To this was added dropwise during a 10 minute period, a solution of 2.2 grams (0.001 mole) of undecanoyl chloride in 50 mL of tetrahydrofuran. The reaction mixture was maintained below about 10° C. throughout the addition. Upon completion of addition, the reaction mixture was stirred under a nitrogen atmosphere for about 4 days. After this time, the reaction mixture was taken up in 100 mL of water and poured into 500 mL of water. The mixture was then extracted with two 200 mL portions of ethyl acetate. The combined extracts were washed with 150 mL of aqueous 10% lithium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. In an effort to remove any excess pyridine, the residue was taken up in 50 mL of toluene, and the solution was concentrated under reduced pressure to a residue. This procedure was repeated two more times. The residue was subjected to column chromatography on silica gel. Elution was accomplished with 10:1 methylene chloride and methanol. The product-containing fractions were combined and concentrated under reduced pressure, yielding 2.8 grams of 2,4-diamino-6-ethyl-5-(4-chloro-3-decylcarbonylaminophenyl)pyrimidine. The NMR spectrum was consistent with the proposed structure.

Quelle