Hydrazine hydrate (1:1) → 6-{2-Amino-6-[2-(trifluoromethyl)-1-pyrrolidinyl]-4-pyrimidinyl}-1H-indazol-3-amine

Participants

Reaction Conditions

Reaction Steps

4-{2-Amino-6-[2-(trifluoromethyl)-1-pyrrolidinyl]-4-pyrimidinyl}-2-fluorobenzonitrile (60 mg, 0.17 mmol) was disolved in ethanol (1.5 mL) with stirring in a 5 mL microwave vessel. Hydrazine monohydrate (0.207 mL, 4.27 mmol) was added, and the mixture was capped and heated at 100° C. in an oil bath overnight. HPLC showed complete conversion. The hot mixture was filtered through a 0.2 um filter disc, rinsing with ethanol (1 mL). Water (˜3 mL) was added to the filtrate with stirring, and the mixture was heated to evaporate most of the ethanol to a volume of ˜4 mL. The mixture was allowed to cool with stirring to room temperature, at which time some product had precipitated as a gum. Stirring was continued for approximately one hour and the precipitate became a free flowing white solid, which was filtered, washed with water and dried to afford the title compound (42 mg) as an off-white solid. LC-MS (ES) m/z=364 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.98-2.08 (m, 2H), 2.08-2.23 (m, 2H), 3.49-3.60 (m, 1H), 3.60-3.72 (m, 1H), 5.06-5.17 (m, 1H), 5.39 (s, 2H), 6.22 (s, 2H), 6.52 (s, 1H), 7.57 (d, J=8.6 Hz, 1H), 7.73 (d, J=8.6 Hz, 1H), 7.94 (s, 1H), 11.54 (s, 1H).

Provenance & Evidence