The general procedure for the synthesis of (E)-4-(dimethylamino)but-2-enoic acid from neratinib maleate SM3-IMP2 was as follows: 1.0 g of the compound obtained in step 1) was dissolved in 6.6 mL of methanol, followed by the addition of 2.2 mL of 40% aqueous sodium hydroxide solution. The reaction mixture was heated to 45 °C and the reaction was stirred at this temperature for 30 minutes. Upon completion of the reaction, the mixture was acidified to pH 2 with a 2-propanol solution of 10% hydrochloric acid, followed by filtration under reduced pressure. The filtrate was concentrated by reduced pressure distillation and then dissolved in 3 mL of 2-propanol, heated to 35°C and stirred for 10 minutes. Next, 3 mL of acetone was added to the solution and the mixture was stirred at 40°C for 30 minutes, followed by continued stirring at room temperature for 12 hours. At the end of the reaction, the resulting solid product was collected by filtration under reduced pressure, washed with a solvent mixture of 2-propanol and acetone (1:2, v/v), and finally dried under reduced pressure to afford the target product (E)-4-(dimethylamino)but-2-enoic acid (500 mg, 54% yield). The structure of the product was confirmed by 1H-NMR (300 MHz, DMSO-d6): δ 6.85 (m, 1H), 6.18 (m, 1H), 3.87 (d, 2H), 2.69 (s, 6H).
