反応 #6625

反応方程式

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

溶媒

triethylamine

acetonitrile

反応条件

後処理

1. 1
   温度is heated
2. 2
   温度at reflux under nitrogen
3. 3
   温度the reaction mixture is heated
4. 4
   温度at reflux under nitrogen for an additional 12 hours
5. 5
   濃縮The reaction mixture then is concentrated under reduced pressure
6. 6
   その他the residue chromatographed on silica gel
7. 7
   洗浄eluting 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
    ろ過The solid which forms is collected by filtration
11. 11
    洗浄washed with cold ethyl acetate
12. 12
    その他dried

実験手順

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.

出典