Hydrochloric Acid → 6-(1-Methyl-1H-pyrazol-5-yl)-N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide Hydrochloride

Participants

Reaction Steps

6-Bromo-N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (169 mg, 0.301 mmol), 5-(1,5-dimethyl-2,4-dioxa-3-borabicyclo[3.1.0]hexan-3-yl)-1-methyl-1H-pyrazole (75 mg, 0.391 mmol) and cesium carbonate (392 mg, 1.204 mmol) in DME (3209 μL) and water (1284 ul) were combined to give a yellow solution. PdCl2(dppf).CH2Cl2 adduct (6.15 mg, 7.52 μmol) was added and the mixture was heated using microwave radiation at 100° C. for 1 hr. A further portion of PdCl2(dppf).CH2Cl2 adduct (6.15 mg, 7.52 μmol) was added and heating continued using microwave radiation at 100° C. for 1 hr. 5-(1,5-Dimethyl-2,4-dioxa-3-borabicyclo[3.1.0]hexan-3-yl)-1-methyl-1H-pyrazole (75 mg, 0.391 mmol), PdCl2(dppf).CH2Cl2 adduct (6.15 mg, 7.52 μmol) and cesium carbonate (392 mg, 1.204 mmol) were added. The mixture was heated using microwave radiation at 100° C. for 2 hrs. The product was purified by chromatography on silica eluting with 0-20% 2M NH3 in MeOH/DCM followed by a second column using 0-15% 2M NH3 in MeOH/DCM. The resulting residue was dissolved in MeOH/DCM, filtered through a glass fibre filter paper and purified by preparative chromatography eluting with 20-50% MeCN/water (0.1% TFA). The appropriate fractions were partitioned between with NaHCO3 and EtOAc and the organic portion was dried (MgSO4) and concentrated to afford a colourless oil. HCl (1 equiv.) in dioxane was added and trituration with EtOAc/EtOH afforded the title compound as a solid;

Provenance & Evidence