Trifluoroacetic acid → 2-(4-(2-Chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-oxopiperazin-1-yl)acetamide

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Reaction Steps

To solution of 2-((2-chloro-5-cyano-3-(2-oxopiperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 628)(10 mg, 0.018 mmol) in DMF (0.5 mL) was added 2-bromoacetamide (4.85 mg, 0.035 mmol) followed by K2CO3 (29.1 mg, 0.211 mmol) and it was stirred at room temperature for 1 h, LC-MS indicated completion. Purification via flash chromatography (0-10% MeOH in DCM, 12 g) gave 9 mg of the PMB protected product. This was dissolved in 1 mL of dichloroethane and then 1 drop of anisole was added followed by 0.5 mL of TFA. The solution was heated at 60° C. for 1 h. LC-MS indicated completion, and then it was cooled and concentrated. The crude was dissolved in methanol and neutralized with 7N ammonia in methanol. After stirring for 10 min it was concentrated, purification via preparative HPLC gave the title compound as a yellow solid (4.7 mg).

Provenance & Evidence