Lithium hexamethyldisilazane → N-(5-chloro-1-(3-(trifluoromethyl)benzyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide

Temperature

0 °C

A solution of 5-chloro-1-(3-(trifluoromethyl)benzyl)-1H-indazol-4-amine (0.024 g, 0.074 mmol) in THF (0.750 mL) was cooled to −10° C. and LHMDS (0.096 mL, 0.096 mmol) was added. The mixture was stirred for 15 minutes, and ethyl 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (Preparation A; 0.049 g, 0.15 mmol) was added as a THF solution (0.750 mL). The mixture was slowly warmed to 0° C. where it stirred for 3 hours. The reaction was quenched with saturated aqueous NaHCO3 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, 10% MeOH/CH2Cl2 with 1% NH3 (7N MeOH)). The resulting solid was slurried in Et2O and filtered and the solid washed with Et2O and then finally with hexanes to provide the title compound (0.002 g, 4%) as a tan powder. MS (ES+APCI) m/z=612 (M).

1. stirringstirred for 3 hours
2. customThe reaction was quenched with saturated aqueous NaHCO3
3. extractionextracted with CH2Cl2
4. washThe combined organic extracts were washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product was purified by preparative TLC (1 mm, 10% MeOH/CH2Cl2 with 1% NH3 (7N MeOH))
9. filtrationfiltered
10. washthe solid washed with Et2O

ORD record

ord-497e0638236e4978b18c3664027b0b05

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09174981B2