Reaktion #6625

Reaktionsgleichung

3-(3-tetrahydropyr-2-yloxyprop-1-en-1-yl)-4-hydroxy-6-pivaloylaminopyrrolo[2,3-d]pyrimidine

diethyl N-(4-iodobenzoyl)glutamate

tris-(2-methylphenyl)phosphine

ethyl N-(4-iodobenzoyl)glutamate

→

diethyl N-[4-{1-(tetrahydropyr-2-yloxy)-3-(4-hydroxy-6-pivaloylaminopyrrolo[2,3-d]pyrimidin-3-yl)prop-2-en-2yl}benzoyl]glutamate

Lösungsmittel

triethylamine

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturis heated
2. 2
   Temperaturat reflux under nitrogen
3. 3
   Temperaturthe reaction mixture is heated
4. 4
   Temperaturat reflux under nitrogen for an additional 12 hours
5. 5
   EinengenThe reaction mixture then is concentrated under reduced pressure
6. 6
   Sonstigethe residue chromatographed on silica gel
7. 7
   Wascheneluting with 20:1 ethyl acetate
8. 8
   workup.DISSOLUTION) The concentrated material is dissolved in 1:5 ethyl acetate
9. 9
   workup.WAITether and this solution is refrigerated for 15 hours
10. 10
    FiltrationThe solid which forms is collected by filtration
11. 11
    Waschenwashed with cold ethyl acetate
12. 12
    Sonstigedried

Vorschrift

A mixture containing 3.48 g of 3-(3-tetrahydropyr-2-yloxyprop-1-en-1-yl)-4-hydroxy-6-pivaloylaminopyrrolo[2,3-d]pyrimidine, 3.12g (1.2 equiv.) of diethyl N-(4-iodobenzoyl)glutamate, 546 mg (20%) of tris-(2-methylphenyl)phosphine, 201 mg (10%) of palladium acetate and 85.5 mg (5%) of cuprous iodide in 15 ml of triethylamine and 240 ml of acetonitrile is heated at reflux under nitrogen. After 12 hours., 1.17 g of ethyl N-(4-iodobenzoyl)glutamate are added and the reaction mixture is heated at reflux under nitrogen for an additional 12 hours. The reaction mixture then is concentrated under reduced pressure and the residue chromatographed on silica gel, eluting with 20:1 ethyl acetate:hexane. (Any recovered starting material can be recycled through the foregoing procedure.) The concentrated material is dissolved in 1:5 ethyl acetate:ether and this solution is refrigerated for 15 hours. The solid which forms is collected by filtration, washed with cold ethyl acetate and dried to yield diethyl N-[4-{1-(tetrahydropyr-2-yloxy)-3-(4-hydroxy-6-pivaloylaminopyrrolo[2,3-d]pyrimidin-3-yl)prop-2-en-2yl}benzoyl]glutamate.

Quelle