Reaction Steps
Lithium bis(trimethylsilyl)amide (1.3 mL, 1.34 mmol, 1.0 M in THF) was added dropwise to a degassed mixture of (2-(3-chlorobenzyl)pyrrolidin-1-yl)(3-chloroquinoxalin-2-yl)methanone (235 mg, 0.61 mmol), tris(dibenzylideneacetone) dipalladium(0) (28 mg, 5 mol %) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (12 mg, 5 mol %) in anhydrous 1,4-dioxane (5.0 mL) at room temperature under nitrogen, after which the mixture was heated to reflux to stir for 16 h. The cooled mixture was treated with 1 N HCl (2 mL), stirred for 30 min and the adjusted to pH 10 with 2 N sodium hydroxide solution and diluted with brine (100 mL). The mixture was extracted with ethyl acetate (2×150 mL) and the combined organic extracts were washed with brine (100 mL), dried over magnesium sulfate and filtered. The filtrate solvents were removed under reduced pressure and the residue was purified by flash column chromatography on silica gel, eluting with hexanes/ethyl acetate (1:1), to provide (3-aminoquinoxalin-2-yl)(2-(3-chlorobenzyl)pyrrolidin-1-yl)methanone as a brown oil: 1H NMR (400 MHz, CDCl3, ˜2:1 mixture of rotamers) δ 7.88 (d, J=9.5 Hz, 1H, rotamers A and B), 7.67-7.63 (m, 1H, rotamers A and B), 7.49-7.11 (m, 1H, rotamers A and B), 7.34 (s, 1H, rotamer A), 7.28-7.19 (m, 1H, rotamers A and B and 3H, rotamer A), 7.09 (d, J=8.9 Hz, rotamer B), 7.00 (t, J=7.8 Hz, rotamer B), 6.88 (s, 1H, rotamer B), 6.73 (d, J=7.8 Hz, 1H, rotamer B), 6.19 (s, 2H, NH2, rotamer A), 6.08 (s, 2H, NH2, rotamer B), 5.22-5.15 (m, 1H, rotamer B), 4.61-4.54 (m, 1H, rotamer A), 3.96-3.89 (m, 2H, rotamer B), 3.84-3.73 (m, 2H, rotamer A), 3.37 (dd, J=3.3. 12.8 Hz, 1H, rotamer A), 2.95 (dd, J=5.0, 13.4 Hz, 1H, rotamer B), 2.83-2.73 (m, 1H, rotamer A), 2.59-2.53 (m, 1H, rotamer B), 2.07-1.75 (m, 4H, rotamers A and B) ppm; ESI MS m/z 367 [M+H]+.
