Potassium Carbonate → HCID 90386185, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (±)-2-(5-chloro-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclopropanecarbonitrile (50.0 mg, 0.154 mmol) and phenylboronic acid (22.5 mg, 0.185 mmol) in a mixture of 1,4-dioxane (3 mL) and water (0.6 mL) was added 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (14.7 mg, 0.0310 mmol), Pd(OAc)2 (3.46 mg, 0.0150 mmol) followed by K2CO3 (63.8 mg, 0.462 mmol). The resulting suspension was purged with N2 gas for 5 minutes then heated at 100° C. in a sealed tube for 12 h. The reaction mixture was allowed to cool to RT and water (10 mL) was added. The reaction mixture was extracted with EtOAc (2×25 mL) and the combined organic extracts washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (Condition B-101 as described in general methods) to afforded (±)-2-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclopropanecarbonitrile (25.0 mg, 43.9%) as white solid. LCMS Condition B-34: retention time 2.44 min, [M+1]=367.0. HPLC Condition B-5: retention time 8.52 min, purity 99.03%. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.53-1.59 (m, 2H), 2.11-2.16 (m, 1H), 2.56-2.61 (m, 1H), 4.69 (d, J=4.8 Hz, 2H), 6.71 (d, J=2.8 Hz, 1H), 7.18 (t, J=4.4 Hz, 1H), 7.27 (t, J=5.2 Hz, 1H), 7.36 (d, J=7.6 Hz, 1H), 7.42-7.53 (m, 5H), 7.73-7.78 (m, 2H), 8.35 (td, J=1.2 Hz, J=4.0 Hz, 1H).

Provenance & Evidence