Reaktion #2075735

Reaktionsgleichung

2-(4-Chloro-2-fluoro-3-methoxyphenyl)-6-methoxy-7-methyl-7H-purine

thionyl chloride

sodium hydroxide

DMF

sodium hydroxide

HCl

→

title compound

Ausbeute 49.3%

6-Chloro-2-(4-chloro-2-fluoro-3-methoxyphenyl)-7-methyl-7H-purine

Ausbeute 49.3%

Lösungsmittel

ethyl acetate

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturheated
2. 2
   Temperaturat reflux for 2 h
3. 3
   TemperaturAfter cooling
4. 4
   FiltrationThe precipitated material was collected by filtration
5. 5
   Waschenwashed with water
6. 6
   Sonstigedried under vacuum at 80° C
7. 7
   TemperaturThe mixture was heated
8. 8
   Temperaturat reflux for 3 h
9. 9
   Temperaturcooled
10. 10
    Waschenwashed twice with water, once with brine
11. 11
    Sonstigedried
12. 12
    Sonstigeevaporated

Vorschrift

2-(4-Chloro-2-fluoro-3-methoxyphenyl)-6-methoxy-7-methyl-7H-purine (1.0 g, 3.1 mmol) was combined with 10 mL 6M HCl and heated at reflux for 2 h. After cooling, the mixture was diluted with 15 mL water and the pH was adjusted to 2 by addition of 2M aqueous sodium hydroxide. The precipitated material was collected by filtration, washed with water and dried under vacuum at 80° C. A 500 mg sample of the crude intermediate was slurried in chloroform (10 mL), treated with DMF (0.62 mL, 580 mg, 8.0 mmol) and then with thionyl chloride (0.58 mL, 950 mg, 8.0 mmol). The mixture was heated at reflux for 3 h, cooled and poured into 20 mL of ice-water. The pH was adjusted to 10 by addition of 1M sodium hydroxide. The precipitated product was taken up in ethyl acetate, washed twice with water, once with brine, dried and evaporated to give the title compound (500 mg, 49% yield over two steps): mp 184-186° C.: 1H NMR (DMSO-d6) δ 8.8 (s, 1H), 7.8 (dd, 1H), 7.46 (dd, 1H), 4.11 (s, 3H), 3.96 (s, 3H).

Quelle