Hydrochloric Acid → HCID 178494714, compound

Participants

Reaction Conditions

Reaction Steps

4-((2-(3-(Methoxymethyl)-1H-indazol-6-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)methyl)piperazin-2-one. 6 M HCl in water (0.410 mL, 2.459 mmol) was added to a stirred mixture of 4-((2-(3-(methoxymethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-ylamino)-[1,2,4]triazolo[1,5-c]pyridin-5-yl)methyl)piperazin-2-one (0.132 g, 0.246 mmol) in ethanol (5 mL) at 60° C. The resulting mixture was stirred vigorously and heated at 60° C. under a reflux condenser under nitrogen for 12 h. The solvent was removed on a rotary evaporator. The residue was dissolved in hot DMSO, diluted with methanol, filtered, and purified using reverse-phase semi-preparatory HPLC (5-30% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 30 min). Fractions containing the desired product were loaded onto a Strata X—C ion exchange column from Phenomenex. The column was washed successively with water, acetonitrile, methanol, and then 5% ammonium hydroxide in methanol. The product came off with the 5% ammonium hydroxide in methanol eluent and was concentrated on a rotary evaporator and dried under high vacuum at 45° C. to give the desired product (0.012 g, 0.030 mmol, 12% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 12.67 (s, 1H), 9.86 (s, 1H), 8.19 (d, J=1.17 Hz, 1H), 7.86 (s, 1H), 7.51-7.65 (m, 3H), 7.24 (dd, J=1.76, 8.79 Hz, 1H), 7.11 (d, J=7.03 Hz, 1H), 4.66 (s, 2H), 4.11 (s, 2H), 3.29 (s, 3H), 3.17-3.27 (m, 4H), 2.80 (t, J=5.27 Hz, 2H); MS (ESI) m/z 407.5 [M+1]+.

Provenance & Evidence