With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.438631-77-7,(R)-1-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate,as a common compound, the synthetic route is as follows.
To degassed mixture of 68 1,4-dioxane (74.3 ml) and 56 DIPEA (5.86 ml, 33.66 mmol) at rt was added 528 7-bromo-4-chloro-6,8-dimethyl-3-nitroquinoline (3.54 g, 11.22 mmol) followed by 272 1-tert-butyl 3-methyl (3R)-piperazine-1,3-dicarboxylate (4.11 g, 16.83 mmol). The reaction was heated at 100 C. for 48 h. The reaction was then cooled to rt and the solvent was removed in vacuo. The residue was diluted with EtOAc (300 ml) and washed with water (2×250 ml) and brine (100 ml). The organic layer was dried (phase separator) and concentrated in vacuo. The crude product was purified by flash silica chromatography (0 to 50% 57 EtOAc in 58 heptane) to give 530 1-tert-butyl 3-methyl (3R)-4-(7-bromo-6,8-dimethyl-3-nitroquinolin-4-yl)piperazine-1,3-dicarboxylate (4.79 g, 82%) as an orange oil; 1H NMR (400 MHz, DMSO, 30 C.) 1.45 (9H, s), 2.64 (3H, s), 2.88 (3H, s), 3.13-3.21 (1H, m), 3.51 (3H, s), 3.51-3.62 (2H, m), 3.8-3.89 (2H, m), 4.03 (1H, s), 4.31 (1H, s), 8.13 (1H, s), 9.06 (1H, s); m/z: ES+ [M+H]+ 524.9.
438631-77-7, As the paragraph descriping shows that 438631-77-7 is playing an increasingly important role.
Reference：
Patent; ASTRAZENECA AB; Kettle, Jason Grant; Bagal, Sharanjeet; Robb, Graeme Richard; Smith, James Michael; Goldberg, Frederick Woolf; Cassar, Doyle Joseph; Feron, James Lyman; US2019/177338; (2019); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics