Propargyl bromide → 3-(2-Fluoro-4-iodo-phenylamino)-1-prop-2-ynyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

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Reaction Conditions

Reaction Steps

A mixture of 3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (70.0 mg, 0.164 mmol), propargyl bromide (80% in xylene, 45.5 μL, 0.41 mmol, 2.5 eq), DBU (3.2 mL), and anhydrous THF (3.2 mL) was stirred at 50° C. under N2 for 1 h, and then at ambient temperature for 17 h. The solvent was evaporated and the resultant residue was diluted with ethyl acetate (75 mL). The organic layer was washed with water (20 mL), followed by brine (20 mL), dried (Na2SO4), filtered and evaporated to give a brown oil. The oil was purified by flash column chromatography (silica, ISCO, 45 mL/min, Hexane:EtOAc, gradient 100:1 to 1:100). Crystallization from EtOAc-hexane gave the desired compound as a yellow solid (34.5 mg, 45.3%). 1H NMR (400 MHz, CDCl3) δ ppm 8.74 (s, 1H), 8.44 (d, J=5.87 Hz, 1H), 7.60 (s, 1H), 7.45 (dd, J=10.26 Hz, 2.0 Hz, 1H), 7.37-7.27 (m, 2H), 6.87 (t, J=9.20 Hz, 1H), 5.29 (s, 2H), 4.46 (q, J=7.14 Hz, 2H), 2.29 (t, J=2.47 Hz, 1H), 1.49-1.40 (t, J=7.20 Hz, 3H); LC-MS (method D): [M+H]+=464.0, RT=2.40 min.

Provenance & Evidence