1,2-Dichloroethane → HCID 57813495, compound

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Reaction Steps

To 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine (0.1 mmol) and 2,3-naphthalenedicarboxylic acid (0.1 mmol) was dissolved in DCM (3 mL) was added HOBt (1.0 eq, 14.0 mg) and EDC (1.0 eq, 19.0 mg). The resultant solution was stirred overnight. The solution was purified by preparative hplc (Gilson) to yield 3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-naphthalenecarboxylic acid. This compound was dissolved in 3 mL of DCM with 1,1-dimethylethyl (2S)-4-{[5′-(aminomethyl)-2′-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate (41.3 mg, 0.1 mmol) to which was added HOBt (1.0 eq, 14.0 mg) and EDC (1.0 eq, 19.0 mg). The resultant solution was stirred overnight and purified by preparative hplc (Gilson) to give 1,1-dimethylethyl (2S)-4-[(5′-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-naphthalenyl}carbonyl)amino]methyl}-2′-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate. This compound was then dissolved in 2 mL of dioxane:MeOH (3:1). Three drops of HCl (concentrated) were added to the resultant solution and it was heated at 60° C. for 1 h. The solution was applied to an amine column which was rinsed with 10 mL of dioxane:MeOH (3:1) to afford 2.7 mg (3.4%) of the above named product. LC-MS m/z 798 (M+H)+, 1.42 min (ret time).

Provenance & Evidence