Phosphoric Acid → HCID 86708588, compound

Participants

Reaction Steps

To a stirred solution of methyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-((methylthio)methoxy)piperidin-4-yl)carbamate (18 mg, 0.032 mmol) in THF (2 mL) at 0° C. was added NIS (14.18 mg, 0.063 mmol) followed by crystalline phosphoric acid (15.44 mg, 0.158 mmol) and allowed to warm to room temperature in 1 h. After TLC showed completion of starting material, reaction mixture was diluted with methanol (2 ml) and treated with 1M Na2S2O3 until it becomes colorless, then pH adjusted to 10 (approx) by addition of solid Na2CO3. Resultant precipitate was removed by filtration and submitted for LC-MS, which showed major product. The filtrate was concentrated and lyophilized to give crude off white solid. This was purified by reverse phase preparative HPLC to give pure sodium (((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4-((methoxycarbonyl)amino)piperidin-3-yl)oxy)methyl phosphate (9 mg) as an off white solid.

Provenance & Evidence