N,N-Diethyl-2,3-dimethylbenzamide → 4-({Methyl-[4-(5-methyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzoyl]-amino}-methyl)-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

N,N-Diethyl-2,3-dimethyl-benzamide (200 mg, 0.97 mmol) was dissolved in anhydrous THF (4 mL) under a N2 and cooled to −78° C. n-BuLi (2.5M in n-hexanes, 0.82 mL, 2.04 mmol) was added dropwise to yield a deep red coloured solution and the reaction mixture was stirred at −78° C. for 30 minutes. 4-{[(4-Cyano-benzoyl)-methyl-amino]-methyl}-piperidine-1-carboxylic acid tert-butyl ester (348 mg, 0.97 mmol) was dissolved in anhydrous THF (4 mL) and added dropwise, and the reaction stirred at −78° C. for 2 h. The reaction mixture was quenched with ice/water, allowed to warm to RT and extracted with CH2Cl2 and EtOAc. The combined organic phase was passed through a phase separation cartridge and concentrated in vacuo. The crude compound was triturated with isohexane/diethyl ether (80:20), the solid filtered and dried in vacuo to give 4-({methyl-[4-(5-methyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzoyl]-amino}-methyl)-piperidine-1-carboxylic acid tert-butyl ester as a light beige solid (171 mg, 36%).

Provenance & Evidence