Reaktion #982576

Reaktionsgleichung

hydrochloride

2-amino-5-(4-chlorophenoxy)-4-(4-oxocyclohexylamino)pyrimidine

Acetic anhydride

pyridine

2-amino-5-(4-chlorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine

→

2-amino-5-(4-chlorophenoxy)-4-(4-oxocyclohexylamino)pyrimidine hydrochloride

Ausbeute 41.0%

Lösungsmittel

dichloromethane

dichloromethane

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooled
2. 2
   workup.STIRRINGThe mixture was stirred for 1.25 hours
3. 3
   workup.STIRRINGstirred for 15 minutes
4. 4
   Filtrationfiltered through a pad of CELITE 545 (Fisher)
5. 5
   FiltrationThe filtrate was filtered
6. 6
   Filtrationthrough flutted filter paper
7. 7
   Sonstigespin evaporated in vacuo
8. 8
   SonstigeThe residue was purified by flash column chromatography on Silica Gel 60 (E. M. Science, 230-440 mesh) (2×16 cm)
9. 9
   Sonstigewere spin evaporated in vacuo
10. 10
    Sonstigeto give a syrup
11. 11
    SonstigeThe residue was triturated under ethyl acetate
12. 12
    Sonstigeto give a white solid which
13. 13
    Sonstigewas collected
14. 14
    Waschenwashed with ethyl acetate
15. 15
    Sonstigedried in vacuo

Vorschrift

Acetic anhydride (0.61 g, 5.8 mmoles) and pyridine (0.96 g, 11.9 mmoles) were added to an ice-bath cooled suspension of chromium(IV) oxide (Aldrich) (0.61 g, 6.1 mmoles) in dichloromethane (11 mL). The mixture was stirred at ambient temperature for 20 minutes, and 2-amino-5-(4-chlorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine (0.65 g, 1.87 mmoles) was added, followed by dichloromethane (10 mL). The mixture was stirred for 1.25 hours and poured into cold ethyl acetate (200 mL), stirred for 15 minutes and filtered through a pad of CELITE 545 (Fisher). The filtrate was filtered through flutted filter paper and then spin evaporated in vacuo. The residue was purified by flash column chromatography on Silica Gel 60 (E. M. Science, 230-440 mesh) (2×16 cm) using ethyl acetate as the eluant. The fractions that contained homogeneous product were spin evaporated in vacuo to give a syrup. The flash column chromatography was repeated. The pure 2-amino-5-(4-chlorophenoxy)-4-(4-oxocyclohexylamino)pyrimidine was converted to the hydrochloride by the same procedure described in Example 4. The residue was triturated under ethyl acetate to give a white solid which was collected, washed with ethyl acetate and dried in vacuo to give 0.29 g (41% yield) of 2-amino-5-(4-chlorophenoxy)-4-(4-oxocyclohexylamino)pyrimidine hydrochloride as a white solid. [Method modeled after M. J. Robins et al. J. Med. Chem., 35, 2283-2293 (1992)]

Quelle