General methodology: to synthesize N-benzyl-4-chloro-N-cyclohexylbenzamide (Compound 1), cyclohexylamine (0.5 M in methanol) was first mixed with benzaldehyde (0.5 M in methanol) and stirred for 3 hrs at 64 °C. Upon completion of the reaction, the mixture was cooled to room temperature, followed by the addition of sodium cyanoborohydride (0.5 M ethanol solution) in two additions, each followed by stirring at room temperature for 30 minutes. Next, the reaction mixture was reheated to 64 °C with continuous stirring for 6 hours. At the end of the reaction, the reaction was quenched with water and extracted three times with dichloromethane. The organic phases were combined, dried with magnesium sulfate and subsequently concentrated under vacuum. The resulting secondary amine was dissolved in anhydrous dichloromethane and mixed with p-chlorobenzoyl chloride. Assuming 100% yield of secondary amine, dimethylaminopyridine (0.1 eq.) dissolved in anhydrous dichloromethane was added to the secondary amine solution, followed by diisopropylethylamine (1.1 eq.). The reaction mixture was purged with nitrogen and sealed and stirred at room temperature overnight. Upon completion of the reaction, the mixture was concentrated under vacuum to an oil, redissolved and purified by reverse phase preparative HPLC (isocratic elution conditions: 75% acetonitrile, 25% water). After purification, the purity of the compounds was determined using reversed-phase analytical HPLC to ensure an average purity greater than 95% (see Supplementary Table 1). Compound 1 was characterized by the following data: IR (CDCl3 film): 2935, 2858, 2246, 1624, 1495, 1418, 1091, 908, 838, 734 cm-1 ; 1H NMR (400 MHz, CDCl3) δ 7.52 (4H), 7.36 (4H), 7.20 (2H), 4.55 (1H) , 3.65 (1H), 1.80 (4H), 1.47 (4H), 1.06 (2H); 13C NMR (75 MHz, CDCl3) δ 171.2, 142.5, 139.0, 135.2, 128.7, 128.4, 127.7, 126.8, 77.17, 59.4, 59.4, 44.6, 32.0 , 30.8, 25.7, 25.1, 25.1, 9.29; HRMS m/z calculated value (M + H)+: 328.1390, measured value: 328.1477.
