Hydrochloric Acid → 2-Amino-5-(4-chlorophenoxy)-4-(4-oxocyclohexylamino)pyrimidine hydrochloride

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Reaction Steps

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)]

Provenance & Evidence