With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.192130-34-0,tert-Butyl 4-(2-aminoethyl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.
192130-34-0, Method B. (i) In a 100 mL three-neck round-bottom flask was charged 2-chloronicotinic acid 1 (0.3151 g, 2.0 mmol), HOBt (0.4054 g, 3.0 mmol), and EDAC (0.5751 g, 3.0 mmol) were dissolved in CH 2 Cl 2 (10 mL). After stirring for 10 min, 4-(2-aminoethyl)-1-boc-piperazine (0.4586 mL, 2.0 mmol) was added followed by Et 3 N (0.5733 mL, 4.0 mmol) and the reaction mixture stirred at room temperature for 16 h. After completion of the reaction, the solution was washed with water (30 mL), and the product was extracted with CH 2 Cl 2 (3 X 20 mL). The combined organic phases were washed with brine, and dried over anhydrous Na 2 SO 4 , filtered, and concentrated under reduced pressure. The concentrated crude oil tert-butyl 4-(2-(2-chloronicotinamido)ethyl)piperazine-1-carboxylate intermediate was obtained (0.63 g, 1.71 mmol, 86%). The product was used in the next step without further purification. Step (ii) In a 100 mL three neck round bottom flask equipped with a stirring bar and reflux condenser, tert-butyl 4-(2-(2 chloronicotinamido)ethyl)piperazine-1-carboxylate (0.630 g, 1.71 mmol) and 9-ethyl-9H-carbazol-3-amine (0.0361 g, 1.72 mmol) were dissolved in 5 mL of DMSO. To the solution, CuI (0.0651 g, 0.3 mmol) and Cs 2 CO 3 (1.11 g, 3.42 mmol) were added and heated at 90 C for 24 hr. After the reaction was complete (analyzed by TLC), the mixture was allowed to reach room temperature. The mixture was washed with water (30 mL), and extracted with CH 2 Cl 2 (3 X 30 mL). The combined organic phases were washed with brine and dried over anhydrous Na 2 SO 4 , filtered, and concentrated under reduced pressure. The crude oil was purified via column chromatography over silica gel and the product 4b was obtained as a white solid (0.08g, 0.15 mmol, 9%). TLC analysis in CH 2 Cl 2 -MeOH (9:1), R f =0.44. 1 H NMR (400 MHz, CDCl 3 ) delta 1.26 (4H, t, J = 7.1 Hz), 1.42 (3H, t, J = 7.3 Hz), 1.46 (9H, s), 1.65 (3H, s), 2.04 (2H, s), 2.48 (3H, t, J = 4.6 Hz), 2.65 (2H, t, J = 5.9 Hz), 3.47 (4H, t, J = 5.3 Hz), 3.56 (2H, q, J = 5.6 Hz), 4.11 (1H, q, J = 7.1 Hz), 4.34 (2H, q, J = 7.6 Hz) 6.64(1H, q, J = 4.8 Hz), 7.19 (1H, t, J = 6.3 Hz), 7.26 (1H, s,), 7.35 (1H, d, J = 4.3 Hz), 7.39 (1H, d, J = 3.8 Hz), 7.43 (1H, t, J = 7.6 Hz), 7.65 (1H, d, J = 1.8 Hz), 7.67 (1H, t, J = 2.3 Hz), 7.69 (1H, d, J = 2.0 Hz), 8.08 (1H, d, 7.6 Hz), 8.31 (1H, d, J = 1.5 Hz), 8.32 (1H, d, J = 1.8 Hz), 8.33 (1H, d, J = 2.0 Hz), 10.40 (1H, s); 13 C NMR (100 MHz, CDCl 3 ) delta 13.8, 37.5, 42.2, 44.8, 45.5, 66.6, 108.3, 112.8, 115.3, 118.3, 120.5, 120.7, 122.8, 123.2, 125.4, 131.6, 132.8, 136.5, 132.0, 140.3, 147.6, 167.8. GC-MS m/z (rel%): [M] 542 (0.01), [M-C 17 H 19 N 3 O] 281 (67.5), [M-C 12 H 23 N 3 O 3 ] 257 (2.6), [M-C 11 H 17 N 3 O] 207 (100).
192130-34-0 tert-Butyl 4-(2-aminoethyl)piperazine-1-carboxylate 1514400, apiperazines compound, is more and more widely used in various fields.
Reference£º
Article; Vlaar, Cornelis P.; Castillo-Pichardo, Linette; Medina, Julia I.; Marrero-Serra, Cathyria M.; Velez, Ericka; Ramos, Zulma; Hernandez, Eliud; Bioorganic and Medicinal Chemistry; vol. 26; 4; (2018); p. 884 – 890;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics