Dimethylformamide → HCID 58529899, compound

Participants

Reaction Steps

A mixture of 5-(2-benzyl-2H-indazol-6-yl)-7-piperidin-4-ylpyrrolo[2,1-f][1,2,4]triazin-4-amine (100 mg, 0.24 mmol), 1-(Boc-aminomethyl)-cyclopropyl-1-carboxylic acid (61 mg, 0.28 mmol), EDCl (50 mg, 0.26 mmol), HOBt (35 mg, 0.26 mmol), and N, diisopropylethylamine (123 μL, 0.71 mmol) in DMF (1.5 mL) was stirred at rt for 17 h. Additional 1-(Boc-aminomethyl)-cyclopropyl-1-carboxylic acid (30 mg), EDCl (25 mg), HOBt (18 mg) and N,N-diisopropylethylamine (62 μL) were added and the mixture continued to stir at rt for 16 hr. The crude mixture was purified by preparative HPLC using a gradient elution from 15% to 45% acetonitrile in water followed by filtration through an acidic resin, washing with MeOH. The product was eluted with 2M NH3 in MeOH and the filtrate was concentrated. To a solution of the residue in MeOH (1 mL) was added 4M HCl in dioxane (500 μL). The mixture was stirred at rt for 64 h. The mixture was concentrated and the residue was dissolved in 3:1 CHCl3/isopropanol (15 mL). The mixture was washed with saturated, aqueous NaHCO3 (15 mL), brine, dried (Na2SO4) and concentrated to dryness to afford 9 mg (8%) of the desired product. 1H NMR (400 MHz, CD3OD) δ 8.36 (s, 1 H), 7.78-7.88 (m, 2 H), 7.65 (s, 1 H), 7.29-7.37 (m, 5 H), 7.22 (dd, 1 H), 6.66 (s, 1 H), 5.65 (s, 2 H), 4.69-4.82 (m, 1 H), 4.44 (br s, 1 H), 3.37-3.51 (m, 1 H), 3.05 (dd, 1 H), 2.94 (br s, 2 H), 2.75 (d, 1 H), 2.21 (d, 1 H), 1.83-2.03 (m, 2 H), 1.60-1.75 (m, 1 H), 0.72-1.06 (m, 4 H); ES-MS m/z 521.21 [M+H]+, HPLC RT (min) 2.30.

Provenance & Evidence