تفاعل #6625

معادلة التفاعل

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

المذيبات

triethylamine

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةis heated
2. 2
   درجة الحرارةat reflux under nitrogen
3. 3
   درجة الحرارةthe reaction mixture is heated
4. 4
   درجة الحرارةat reflux under nitrogen for an additional 12 hours
5. 5
   تركيزThe reaction mixture then is concentrated under reduced pressure
6. 6
   أخرىthe residue chromatographed on silica gel
7. 7
   غسيلeluting 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
    ترشيحThe solid which forms is collected by filtration
11. 11
    غسيلwashed with cold ethyl acetate
12. 12
    أخرىdried

الإجراء التجريبي

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.

المصدر