2-(4-Amino-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl)-cyclopropanecarboxylic acid ethyl ester → 2-(4-Amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl)-cyclopropanecarboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(4-amino-pyrrolo[2,1-f][1,2,4]triazin-7-ylmethyl)-cyclopropanecarboxylic acid ethyl ester (4.5 g, 17.2 mmol) in THF (73 mL) cooled to −20° C. was added 2,5-dibromo-4,4-dimethyl-cyclopentane-1,3-dione (2.4 g, 8.6 mmol) in four portions over 15 mins. The mixture was allowed to stir at −20° C. for 2 hours. The mixture was quenched with sodium thiosulfate solution (20 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (100 mL). The combined organic layer was washed with water, brine, dried by Na2SO4, filtered and concentrated. The residue was purified by Biotage® to give 3.0 g (51%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 7.80 (s, 1 H), 8.75 (bs, 2 H), 6.60 (s, 1 H), 4.0 (m, 2 H), 2.9 (d, 2 H), 1.5 (m, 2 H), 1.2 (t, 3 H), 1.0 (m, 2 H); ES-MS m/z 339.19 [M+H]+, HPLC RT (min) 2.58.

Provenance & Evidence