3-Butyn-1-OL → 4-(4-Aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)but-3-yn-1-ol

Participants

Reaction Conditions

Reaction Steps

To a solution of 7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine (2.25 g, 10.6 mmol), tetrakis(triphenylphosphine)palladium(0) (610 mg, 0.53 mmol), and copper(I) iodide (500 mg, 2.64 mmol) in degassed pyrrolidine (45 mL) was added 3-butyn-1-ol (1.6 mL, 21.1 mmol), dropwise. The reaction was heated (50° C.) for 17 h. After cooling to rt, saturated aqueous ammonium chloride solution was added (50 mL) and the mixture was extracted first with ethyl acetate (4×50 mL) then with 3:1 chloroform/isopropanol (5×100 mL). The organics were separately dried (Na2SO4) and the solvent was evaporated. The combined crude oils were purified via flash chromatography on silica gel eluting with 100% ethyl acetate, followed by trituration with ethyl acetate to obtain 1.3 g (61%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 7.85 (s, 1 H), 7.81 (br s, 2 H), 6.82 (d, 1 H), 6.75 (s, 1 H), 4.91 (t, 1 H), 3.58 (q, 2 H), 2.63 (t, 2 H); ES-MS m/z 203.2 [M+H]+, HPLC RT (min) 1.05.

Provenance & Evidence