Lithium Chloride → N-(6-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyrazin-2-yl)acetamide

Participants

Reaction Conditions

Reaction Steps

A solution of N-(6-chloropyrazin-2-yl)acetamide (77.0 mg, 0.447 mmol) and hexamethylditin (0.124 mL, 0.596 mmol) in 1,4-dioxane (15 mL) was purged with argon gas for 30 min. Pd(Ph3P)4 (34.0 mg, 0.0300 mmol) was added and the reaction mixture was heated at 100° C. for 1 h. Then the reaction mixture was allowed to cool to RT and then 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (0.100 g, 0.298 mmol) was added followed by LiCl (13.0 mg, 0.298 mmol). The reaction mixture was heated at 100° C. for 12 h. The cooled reaction mixture was filtered through the CELITE® and washed with ethyl acetate (10 mL). The filtrate was evaporated under reduced pressure to give a residue which was purified by preparative TLC plate (40% ethylacetate/petroleum ether) then further purified by preparative HPLC (Condition B-100 as described in general methods) to give N-(6-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyrazin-2-yl)acetamide (20.0 mg, 15.4%). LCMS Condition B-34: retention time 2.27 min, [M+1]=437.0. HPLC Condition B-5: retention time 6.86 min, purity 97.45%. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.18 (s, 3H), 4.93 (d, J=4.5 Hz, 2H), 6.85-6.88 (m, 1H), 7.29 (ddd, J=7.5 Hz, J=5.0 Hz, J=1.0 Hz, 1H), 7.38 (t, J=4.5 Hz, 1H), 7.46-7.50 (m, 2H), 7.52-7.57 (m, 2H), 7.58-7.63 (m, 2H), 7.79 (td, J=7.7 Hz, J=1.8 Hz, 1H), 7.89 (d, J=2.5 Hz, 1H), 8.39 (td, J=2.5 Hz, J=1.0 Hz, 1H), 9.17 (s, 1H), 9.43 (s, 1H), 11.15 (s, 1H).

Provenance & Evidence