Sodium Hydroxide → N-[(4-fluoro-3'-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]-3-(4-piperidinylmethyl)benzamide

Participants

Reaction Steps

To a solution of 1,1-dimethylethyl (2S)-4-{[3′-(aminomethyl)-4′-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate (0.108 g, 0.261 mmol) in DMF (2.5 mL) was added the commercially available 3-[(1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-piperidinyl)methyl]benzoic acid (0.083 g, 0.261 mmol), HATU (0.110 g, 0.290 mmol), and diisopropylethylamine (0.10 mL, 0.574 mmol). The reaction was allowed to stir at room temperature for 2 days. The reaction was diluted with EtOAc (75 mL), washed with 1N HCl (2×20 mL), then saturated NaHCO3 (3×20 mL), then brine (2×20 mL). The organic layer was dried over MgSO4, filtered, and concentrated under vacuum. The residue was taken up in MeOH (4 mL) and HCl (4N in 1,2-dioxane, 2.5 mL) was added. The reaction was allowed to stir at room temperature overnight. The reaction was concentrated under vacuum, and the residue was taken up in 1 DMSO/1 MeOH and purified via MDAP (10-90% CH3CN/H2O/(0.1% TFA)). The desired fractions were isolated, and then taken up in DCM (8 mL) and 1N NaOH (8 mL) and allowed to stir for 1 hour. The DCM was isolated using a phase separator and then concentrated under vacuum to give the title compound (84.6 mg, 67.1%). El-MS m/z 515(M−H)+.

Provenance & Evidence