1,2-Dichloroethane → 4-[6-(4-Hydroxy-phenyl)-3-((E)-styryl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid dimethylamide

Participants

Reaction Conditions

Reaction Steps

0.24 mmol of piperazine-1-carboxylic acid dimethylamide were weighted into a reaction tube and dissolved/suspended in 1 ml THF. 1 ml of a DMF stock solution containing 0.24 mmol of 6-(4-Hydroxy-phenyl)-3-((E)-styryl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid, 1 mmol N-methyl morpholine, 0.01 mmol 4-dimethylaminopyridine, and 0.3 mmol 1-hydroxybenzotriazole were added, followed by 0.3 mmol EDC. The tube was closed and shaken at 50° C. overnight. The THF was left to evaporate, 0.1 ml TFA was added, the volume was adjusted to 2 ml with DMF. The solution was filtered and submitted to prep. RP HPLC purification to give 4-[6-(4-Hydroxy-phenyl)-3-((E)-styryl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid dimethylamide. In order to transform the trifluoro acetic acid salt into a hydrochloric acid salt and—for other examples to cleave acid labile protecting groups—the product obtained above was shaken with 3 ml methanol and 0.5 ml 4M HCl in dioxane at 65° C. for 30 minutes. Then 10 ml diethyl ether was slowly added to the cooled solution, and the formed precipitate was filtered off, washed with 1 ml diethyl ether, and dried in vacuo to afford 0.085 mmol of 4-[6-(4-Hydroxy-phenyl)-3-((E)-styryl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid dimethylamide (35%).

Provenance & Evidence