Acetic Acid → HCID 58529679, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-(2-benzyl-2H-indazol-6-yl)-7-(2-piperidin-4-yl-1,3-thiazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine hydrochloride (100 mg, 0.17 mmol) in MeOH (2 mL) containing 3 Å molecular sieves was added AcOH (99 μL, 1.73 mmol), [(1-ethoxycyclopropyl)oxy]trimethylsilane (180 mg, 1.04 mmol) and sodium cyanoborohydride (49 mg, 0.78 mmol). The reaction was stirred at 60° C. for 17 h. Aqueous NaOH (1N, 5 mL) was added and the mixture was extracted with EtOAc (2×10 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated. The residue 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 provide 19 mg (21%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.57 (s, 1 H), 8.35 (s, 1 H), 8.09 (s, 1 H), 7.83 (d, 1 H), 7.67 (s, 1 H), 7.28-7.41 (m, 5H), 7.18-7.23 (m, 2 H), 5.67 (s, 2 H), 2.95-3.09 (m, 3 H), 2.30 (t, 2 H), 2.05 (d, 2 H), 1.57-1:72 (m, 3 H), 0.37-0.45 (m, 2 H), 0.25-0.34 (m, 2 H); ES-MS m/z 547.21 HPLC RT (min) 2.39.

Provenance & Evidence