Hydrochloric Acid → HCID 178508527, compound

Participants

Reaction Steps

4-Chloro-5-(4-chlorophenoxy)-2-(diisopropylaminomethyleneamino)pyrimidine (3.68 g, 0.01 mole) and trans-4-aminocyclohexanol hydrochloride (5.31 g, 0.035 mole) were combined in absolute ethanol (25 mL). Triethylamine (7.08 g, 0.07 mole) was added, and the mixture was refluxed with stirring for 56 hours when thin layer chromatography confirmed the absence of the starting pyrimidine. The mixture was cooled slightly, concentrated hydrochloric acid (5 mL) was added and reflux was resumed for an additional 2 hours. The mixture was spin evaporated in vacuo. The oily residue was dissolved in water (200 mL) and extracted with dichloromethane (2×200 mL). The aqueous phase was basified with 2 M sodium hydroxide to pH 9, and the gummy residue that precipitated was dissolved in dichloromethane (100 mL). The aqueous phase was back washed with dichloromethane (100 mL), and the combined organic extracts were washed with brine (200 mL), dried over sodium sulfate, filtered and spin evaporated in vacuo to a foam. This material was dissolved in ethyl acetate and chromatographed on Silica Gel 60 (E. M. Science, 230-440 mesh) (8 g; 2×7 cm column bed) using ethyl acetate as eluent. The first 100 mL of eluent was collected and spin evaporated in vacuo to give 2.30 g (69% yield) of 2-amino-5-(4-chlorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine as a white powder, mp 154-155° C.

Provenance & Evidence