The general procedure for the synthesis of (2-(phenylamino)-1,4-phenylene)bis((4-(pyrrolidin-1-yl)piperidin-1-yl)methanone) from 2-(phenylamino)terephthalic acid and 4-pyrrolidin-1-yl-piperidine was as follows: 9.0 g of 2-(phenylamino)terephthalic acid was dissolved in 90 mL of N,N-dimethylformamide (DMF), 11.3 g of 1 -hydroxybenzotriazole (HOBt), 16.0 g 1 -ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI-HCl) and 14.2 g triethylamine (Et3N). The reaction was carried out in an ice bath under nitrogen protection for 1 hour. Subsequently, 10.8 g of 4-(1-pyrrolidinyl)piperidine dissolved in 50 mL of DMF was slowly added dropwise to the above reaction mixture and stirred at room temperature overnight. The following day, the completion of the reaction was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the reaction was quenched with water, diluted with 200 mL of water and subsequently extracted with 200 mL of ethyl acetate (EA). The organic phases were combined and the pH of the aqueous phase was adjusted to about 3 with 3 M hydrochloric acid, the organic phase was separated and discarded. The aqueous phase pH was adjusted to 9-10 and the product was extracted with EA. The organic phases were combined, washed three times with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent to give 18 g of crude product. The crude product was recrystallized with ethanol (EtOH)/EA/petroleum ether (PE) mixed solvent to give 16.4 g of white crystalline solid, the target compound (2-(phenylamino)-1,4-phenylene)bis((4-(pyrrolidin-1-yl)piperidin-1-yl)methanone) (UNC1215) in 88.7% yield.
