HCID 16661435, compound → HCID 66673053, compound

Participants

Reaction Steps

A solution of 4-(3-bromo-4-fluorophenyl)-6-phenylpyrimidin-2(1H)-one (0.3 g, 0.9 mmol) and copper(I) cyanide (0.16 g, 1.7 mmol) in N,N-dimethylformamide (3 mL) was heated to 155° C. for 24 hours. The crude reaction mixture was concentrated in vacuo then partitioned between saturated sodium bicarbonate (aqueous) and ethyl acetate/methanol (10:1). The layers were separated and the aqueous layer was extracted once with 10:1 ethyl acetate/methanol. The combined organic layers were dried (sodium sulfate), filtered and concentrated in vacuo to give 0.30 g (quantitative yield) of crude 2-fluoro-5-(2-oxo-6-phenyl-1,2-dihydropyrimidin-4-yl)benzonitrile that was used without further purification for the next step. A solution of 2-fluoro-5-(2-oxo-6-phenyl-1,2-dihydropyrimidin-4-yl)benzonitrile (0.30 g, 1.0 mmol) and hydrazine monohydrate (1.7 mL, 36 mmol) in t-butanol (34 mL) was heated at 120° C. for 12 hours. The solution was concentrated in vacuo to give a solid, which was taken into hot methyl alcohol and treated with an excess of 4.0M hydrogen chloride in dioxane. After concentration in vacuo, the resultant solid was triturated in hot ethyl acetate, collected by vacuum filtration then lyophilized from aqueous solution to give 4-(3-amino-1H-indazol-5-yl)-6-phenylpyrimidin-2(1H)-one dihydrochloride (0.034 g, 11% yield). 1H NMR (400 MHz, DMSO): 8.93 (broad s, 1H), 8.20 (d, 1H), 8.11 (d, 1H), 7.70 (t, 1H), 7.65 (t, 2H), 7.57 (broad s, 1H), 7.47 (d, 1H). MS (EI) for C17H13N5O: 304 (MH+).

Provenance & Evidence