55899-13-3

626-55-1

36016-40-7

55899-13-3

All reactions were carried out using a commercially available Vapourtec R-series device equipped with four pumps. The steps were as follows:(E)-Ethyl N-(homotrimethylbenzenesulfonyl)oxyiminate 7 was dissolved in acetonitrile (MeCN, 1 M) and filtered. Perchloric acid (pure, 11.6 M) was mixed with the first inlet via a Y-mixer at flow rates of 1.228 mL/min and 0.106 mL/min, respectively.3-Bromopyridine 2 was dissolved in acetonitrile (2 M), filtered and introduced into the Y-mixer at a flow rate of 0.614 mL/min. Sodium hydroxide (1 M) was diluted to 0.667 M with N,N-dimethylformamide (DMF) and introduced into a third Y-mixer at a flow rate of 1.840 mL/min. The stoichiometric ratio of all four inlets was 1:1:1:1. The system solvents were acetonitrile in the first three inlets and water/DMF (2:1) in the fourth inlet. The PFA (polyfluoroalkoxyalkane polymer) reactor coils with volumes of 20 mL, 2 mL, and 10 mL, respectively, were all set to 30 °C. Reaction mixtures from the first two inlet streams remained in the first reactor for 15 min, the second for 1.02 min, and the third for 2.64 min. In all cases, the power traces of the third reactor (where amination occurs) show that an exothermic reaction occurs (lower power required for heating to 30 °C). Only the first double pump started with an operating pressure of 7-8 bar, and all four pumps were raised to 9-10 bar. After the reaction was completed, the reaction unit was rinsed with a 33% aqueous solution. Concentrated hydrochloric acid (HCl) was added to methanol (MeOH) followed by isopropanol (IPA). The total flow rate at the outlet was 3.788 mL/min.Synthesis of 1-amino-3-bromopyridin-1-ium 2,4,6-trimethylbenzenesulfonate (3a): 3-bromopyridine 2a was allowed to react with MSH 1 according to a generalized procedure. The exit solution (25 mL, collection over 3.6 min) was concentrated in vacuum to give an orange solid (collection time 3.6 min, purity >99%).1H NMR (400 MHz, d6-DMSO) δ 2.18 (9H, s, 3×CH3), 6.77 (2H, s, NH2), 7.93 (1H, dd, J = 4 and 8 Hz, ArH), and 7.95 (s, 2H, ArH), 8.49 (1H, d, J = 8 Hz, ArH), 8.81 (1H, d, J = 8 Hz, ArH), 9.17 (1H, s, ArH) ppm. 13C NMR (101 MHz, d6-DMSO) δ 20.3, 22.7, 121.4, 128.6, 129.9, 135.8, 136.4, 138.6, 141.4, 142.5, 166.0 ppm. HRMS (FAB) calculated value of C5H6BrN2+ 172.97144, measured value 172.97105; C9H11O3S- 199.04289, measured value 199.04277. DSC analysis showed small exothermic peaks, 61 J/g starts from 249℃, and the amplified exothermic peak, 573 J/g starts from 299℃.