Reaktion #2268541

Reaktionsgleichung

dichloromethane isohexane

1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxo-6-[[2-(trifluoromethyl)phenyl]methyl]-thieno[2,3-d]pyrimidine-5-carboxylic acid

triethylamine

diphenylphosphoryl azide

→

subtitle compound

5-Amino-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Lösungsmittel

tert-butanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe reaction was concentrated in vacuo
2. 2
   workup.DISSOLUTIONthe residue redissolved in dichloromethane (50 ml)
3. 3
   Einengenbefore being concentrated in vacuo, and residual acid
4. 4
   Sonstigewas removed
5. 5
   Sonstigeby azeotroping with toluene
6. 6
   SonstigeThe residue was partitioned between half saturated sodium hydrogen carbonate and dichloromethane
7. 7
   SonstigeThe organics were collected
8. 8
   Trocknendried over magnesium sulfate
9. 9
   Einengenconcentrated in vacuo
10. 10
    SonstigeThe crude product was purified by chromatography
11. 11
    Wascheneluting with 2:1 isohexane
12. 12
    Sonstigediethyl ether to yield a highly crystalline solid which

Vorschrift

1,2,3,4-Tetrahydro-3-methyl-1-(2-methylpropyl)-2,4-dioxo-6-[[2-(trifluoromethyl)phenyl]methyl]-thieno[2,3-d]pyrimidine-5-carboxylic acid made by the method of Example 8a) (3.316 g), triethylamine (1.38 ml) and diphenylphosphoryl azide (2.26 ml) were heated at 90° C. under an atmosphere of nitrogen in tert-butanol for 18 hrs. The reaction was concentrated in vacuo and the residue redissolved in dichloromethane (50 ml) and trifluoroacetic acid (30 ml). The mixture was allowed to stir for 36 hrs before being concentrated in vacuo, and residual acid was removed by azeotroping with toluene. The residue was partitioned between half saturated sodium hydrogen carbonate and dichloromethane. The organics were collected, dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by chromatography, eluting with 2:1 isohexane:diethyl ether to yield a highly crystalline solid which was recystallised from dichloromethane/isohexane to yield the subtitle compound (1.553 g).

Quelle