Lithium Hexamethyldisilazide → 7-(2-(4-methylpiperazin-1-yl)ethoxy)-N-(1-(pyridin-3-ylmethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of 1-(pyridin-3-ylmethyl)-1H-indazol-4-amine (0.040 g, 0.18 mmol) in THF (1.1 mL) was cooled to −10° C. in an ice/salt bath. LHMDS (0.19 mL, 0.19 mmol, 1.0M THF) was added and the mixture was stirred for 15 minutes. To this dark solution was added a THF (1.1 mL) solution of ethyl 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (Preparation A; 0.030 g, 0.090 mmol) at 0° C. The mixture was slowly warmed to 0° C. where it stirred for 3 hours. The reaction was quenched with a saturated aqueous NaHCO3 solution and extracted with CH2Cl2. The combined organic extracts were washed with brine and dried over Na2SO4, filtered and concentrated. The crude product was purified by preparative TLC (1 mm, 15% MeOH/CH2Cl2 with NH3) to afford 0.028 g of 7-(2-(4-methylpiperazin-1-yl)ethoxy)-N-(1-(pyridin-3-ylmethyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide as a tan powder. This material was suspended in MeOH (4.0 mL) and HCl (0.90 mL, 1.8 mmol, 2.0M Et2O) was added. The resulting suspension was stirred for 3 hours and then concentrated. The solid was slurried in Et2O and isolated by vacuum filtration. The solid was dried under vacuum overnight to afford 0.035 g of the title compound (62%). MS (ES+APCI) m/z=511 (M+H-3HCl).

Provenance & Evidence