Chlorotrimethylsilane → 2-[(4-Amino-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-hydroxy-methyl]-cyclopropanecarboxylic acid ethyl ester

Participants

Reaction Steps

To a stirred solution of 7-bromo-pyrrolo[2,1-f][1,2,4]triazin-4-ylamine (5.27 g, 24.7 mmol) in anhydrous THF (40 mL) was added chlorotrimethylsilane (5.9 g, 54.4 mmol) at rt. The reaction mixture was stirred at rt for 2 hours and cooled in an ice water bath. 2-propylmagnesium chloride in THF (52 mL, 104 mmol, 2.0 M) was added dropwise, and the reaction mixture was allowed stirred at rt for 2 hours. The reaction was cooled to 0° C. with an ice bath, and 2-formyl-cyclopropanecarboxylic acid ethyl ester (4.6 g, 32 mmol) was added. The reaction mixture was stirred at rt for 1 hour. The mixture was quenched with saturated, aqueous ammonium chloride (20 mL) In ice water bath. 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 crude product was separated by column (30% EtOAc/70% Hexane) to give 2.0 g (30%) of product. 1H NMR (300 MHz, DMSO-d6) δ 8.80 (s, 1 H), 8.75 (bs, 2 H), 6.80 (s, 1 H), 6.60 (m, 1 H), 5.40 (s, 1 H), 5.0-4.8 (m, 1 H), 4.0 (m, 2 H), 1.9-1.8 (m, 2 H), 1.2 (t, 3 H), 1.0 (m, 2 H); ES-MS m/z 277.34 [M+H]+, HPLC RT (min) 1.51.

Provenance & Evidence