3-Chlorophenol → 5-(3-Chlorophenoxy)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde

Participants

Reaction Steps

Tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate (1.0 eq, 49 mg, 0.145 mmol) was mixed in a vial with NMP (0.2 ml), 3-chlorophenol (5.0 eq, 93 mg, 0.274 mmol) and potassium carbonate (5.0 eq, 100 mg, 0.723 mmol). The reaction mixture was stirred at room temperature for one hour. Water was added and the resulting gummy material was extracted with methylene chloride. The organic phase was dried over Na2SO4 and the volatiles removed in vacuo. The resulting NMP solution was reacted with a HCl 4N solution in dioxane (5 ml) at room temperature for one hour, at which time LCMS monitoring indicated completion of the reaction. The reaction was treated with water and 6N NaOH and stirred overnight at room temperature. The solid was filtered and dried to afford crude 5-(3-chlorophenoxy)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde as a solid (31 mg). The material was heated with hydantoin (30 mg), piperidine (30 uL) in Ethanol (1 ml) in a vial at 90° C. for seven hours. Water was added and the material was filtered, washed with ethanol, ethanol/water and dried. (Z)-5-((5-(3-chlorophenoxy)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-3-yl)methylene)imidazolidine-2,4-dione was isolated as solid (43 mg, 38% over 2 steps).). LCMS (ES):>95% pure, m/z 411 [M+H]+.

Provenance & Evidence