2-(4-propan-2-ylpiperazin-1-yl)ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A one dram vial was charged with solid potassium tert-butoxide (55 mg, 0.49 mmol), 2-(4-isopropylpiperazin-1-yl)ethanol (0.099 g, 0.57 mmol), and tert-butanol (0.3 mL, 3.4 mmol). The mixture was stirred at ambient temperature for 30 minutes. 7-Fluoro-N-(3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (0.034 g, 0.077 mmol) was added in one portion. The mixture was heated at 90° C. with stirring for 16 hours. The mixture was cooled to ambient temperature and diluted with water until a precipitate formed. The precipitate was collected by filtration and dried under high vacuum to give the product (0.019 g). MS (APCI), positive scan, m/z=593.1 (M+H). The mixture was heated at 90° C. with stirring for 16 hours The mixture was cooled to ambient temperature formed The precipitate was collected by filtration dried under high vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 50 mL round bottom flask was charged with solid potassium tert-butoxide (1.7 g, 14.8 mmol), 2-(4-isopropylpiperazin-1-yl)ethanol (2.88 g, 16.7 mmol), and tert-butanol (10 mL, 103 mmol). The mixture was stirred at ambient temperature for 1 hour before heating at 90° C. for 15 minutes to give a homogeneous mixture. 7-Fluoro-N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (1.0 g, 2.3 mmol) was added in one portion. The mixture was heated at 90° C. with stirring for 16 hours. The mixture was cooled to ambient temperature before pouring into a 250 mL round bottom flask containing 150 mL of water. Vigorous stirring at ambient temperature for 2 hours resulted in a beige precipitate. The precipitate was collected by filtration and dried under high vacuum to give the product. MS (APCI), positive scan, m/z=581.1 (M+). before heating at 90° C. for 15 minutes to give a homogeneous mixture The mixture was heated at 90° C. with stirring for 16 hours The mixture was cooled to ambient temperature before pouring into a 250 mL round bottom flask Vigorous stirring at ambient temperature for 2 hours resulted in a beige precipitate The precipitate was collected by filtration dried under high vacuum to give the product

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (60% in mineral oil; 21.00 g; 525 mmol) was added to a 4-neck (2 L) flask under nitrogen with mechanical stirrer, condenser, thermocouple and addition funnel attached. Dry diglyme (450 mL) was added. A solution of 2-(4-isopropylpiperazin-1-yl)ethanol (90.45 g; 525 mmol) in diglyme (150 mL) was added slowly with stirring. The temperature was slowly increased to 40° C. until effervescence had ceased. The mixture was allowed to cool and 4-chloropyridin-2-amine (45.00 g; 350 mmol) was added. The mixture was heated at 157° C. for 16 hours and allowed to cool. Water (300 mL) was added followed by THF (750 mL). Sodium chloride was added (sufficient to saturate the aqueous phase). The phases were separated and the aqueous phase was further extracted with THF (3×600 mL). The combined organic phases were dried with sodium sulfate (600 g) for 16 hours and then filtered. The solvent was removed under vacuum (8 mm Hg, bath temperature at 60° C., to remove the diglyme). The residue was dissolved in THF (1000 mL) and filtered (Celite) to remove some fine particulates. The solvent was removed under vacuum to give a pale brown oil. The material was placed under high vacuum. A solid slowly formed (about 130 g). Ether (200 mL) was added and the material was physically broken up. Hexane (about 200 mL) was added, and the resulting solids were mechanically stirred to break them up. The solids were collected by filtration and washed (hexane/ether 1:1). The material was dried under vacuum to give the desired product (38.4 g) as a cream colored solid. thermocouple and addition funnel to cool The mixture was heated at 157° C. for 16 hours to cool to saturate the aqueous phase) The phases were separated the aqueous phase was further extracted with THF (3×600 mL) The combined organic phases were dried with sodium sulfate (600 g) for 16 hours filtered The solvent was removed under vacuum (8 mm Hg, bath temperature at 60° C. to remove the diglyme) The residue was dissolved in THF (1000 mL) filtered (Celite) to remove some fine particulates The solvent was removed under vacuum to give a pale brown oil A solid slowly formed (about 130 g) the resulting solids were mechanically stirred The solids were collected by filtration washed (hexane/ether 1:1) The material was dried under vacuum