Sodium Hydroxide → N-(3-cyclopropyl-1-((5-hydroxy-6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

To lithium 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (101 mg, 0.318 mmol) was added NMP (5 mL, distilled over oven dried MgSO4). A heat gun was used to dissolve the starting material. The reaction was cooled to 0° C. and 2,4,6-trichlorobenzoyl chloride (50.8 μL, 0.318 mmol) was added dropwise. The cold bath was removed once the addition was complete. The reaction mixture was stirred for one hour. 1-((5-(tert-Butyldimethylsilyloxy)-6-methylpyridin-2-yl)methyl)-3-cyclopropyl-1H-indazol-4-amine (100 mg, 0.245 mmol) was then added in one portion to the reaction mixture and the reaction was heated to 88° C. and stirred for 5 hours. NMP was removed by vacuum distillation until the reaction mixture became a thick oil. NaOH (3 equivalents relative to lithium salt starting material) in H2O (5 mL) was added to the thick oil. The mixture was stirred at 80° C. for 30 minutes. The mixture was cooled to ambient temperature and the pH of the dark solution was adjusted to about pH 12-13 with saturated NH4Cl aqueous solution. The mixture was cooled to 0° C. and H2O (10 mL) was added. Stirring was continued for 30 minutes, during which time a solid started to crash out. The mixture was filtered and the solid was washed with a saturated NaHCO3 solution and H2O. The solid was dissolved in DCM and dried (Na2SO4). The solution was filtered, concentrated and triturated with MTBE give the final product (49%). MS (ES+APCI) m/z=581.4 (M+H).

Provenance & Evidence