29671-92-9,Some common heterocyclic compound, 29671-92-9, name is Carbamimidic chloride hydrochloride, molecular formula is CH4Cl2N2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
General procedure: A solution of 6-chloro-3-nitropicolinonitrile (25) (0.60 g, 2.7 mmol) and an appropriate aniline was heated at 130 C in isopropanol. After 3-16 h, the solution was concentrated under reduced pressure. The precipitate obtained was neutralized with solution of ammonia in methanol to afford 26-38 as a crude product. The next step was carried out without any purification. To a suspension of 26-38 in methanol (20 mL) and concentrated hydrochloric acid (36%, 2 – 4.0 mL) was added iron powder. The mixture was refluxed until all the starting material had reacted (monitored on TLC). The hot reaction mixture was poured into water (20 mL) and stirred for 5 min. The unreacted iron was removed using a stirring bar retriever, and the aqueous solution was neutralized with ammonium hydroxide to pH 4. The solution was then extracted with chloroform (3 ¡Á 20 mL), and the combined organic layer was washed with water (2 ¡Á 5.0 mL), sodium bicarbonate solution (5.0 mL), and brine (5.0 mL) and dried over anhydrous sodium sulfate. The product (39-52) was obtained as a gummy brown semi-solid. The next step was carried out without any purification and characterization. Mixture of 39-52, chloroformamidine hydrochloride (1 g), and dimethyl sulfone (4.0 g) was heated in an oil bath at 140 C under nitrogen for 15 min. The oil bath was removed, and water (10 mL) was added slowly to the hot reaction mixture. The aqueous solution was cooled to room temperature and extracted with chloroform (3 ¡Á 5 mL) to remove dimethyl sulfone. The aqueous phase was made basic to pH 10 with ammonium hydroxide, followed by removal of water under reduced pressure. The residue was dissolved in a mixture of 50:50 methanol-acetone (v/v), and silica gel was added (3.0 g). After the removal of solvent with a rotary evaporator, the silica gel plug was loaded onto a column and eluted with 1:5 MeOH-CHCl3 (v/v). The fractions containing the required compound were evaporated under reduced pressure to afford the targeted compounds.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Carbamimidic chloride hydrochloride, its application will become more common.
Reference:
Article; Shah, Khushbu; Queener, Sherry; Cody, Vivian; Pace, Jim; Gangjee, Aleem; Bioorganic and Medicinal Chemistry Letters; vol. 29; 15; (2019); p. 1874 – 1880;,
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