Lithium Hexamethyldisilazide → HCID 57384604, compound

Participants

Reaction Steps

A solution of 3-((4-amino-1H-indazol-1-yl)methyl)-N,N-dimethylbenzamide (0.15 g, 0.51 mmol) and THF (1.0 mL) was cooled to −5° C. in an ice/brine bath, then LHMDS (0.48 ml, 0.48 mmol, 1.0M THF) was added drop-wise and the mixture was stirred for 10 minutes, during which a dark emulsion formed. Ethyl 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (Preparation A; 0.080 g, 0.24 mmol) was added dropwise as a THF solution (1.0 mL). The reaction was stirred at −5 to 0° C. for 1 hour, then quenched with saturated aqueous NH4Cl (10 mL). The mixture was extracted with CH2Cl2 and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude residue was slurried in Et2O with vigorous stirring and then filtered through a nylon filter providing crude product with >90% purity (0.083 g). The crude product was purified by column chromatography (5 to 20% MeOH/CH2Cl2 using 5% NH4OH/MeOH). The fractions were concentrated and the product dissolved in CH2Cl2 and then filtered. The filtrate was concentrated to provide N-(1-(3-(dimethylcarbamoyl)benzyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide as a pale orange solid (0.060 g). This product was dissolved in MeOH (2.4 mL) and then HCl (2.41 mL, 4.81 mmol, 2.0M Et2O) was added. The mixture was stirred for 2 hours and then concentrated. The resulting solid was washed with Et2O and hexanes and dried under vacuum to provide 0.050 g (31%) of the title product as a pale brown powder. MS (ES+APCI) m/z=581 (M+H-2HCl).

Provenance & Evidence