The main application background and overview of 5-bromo-[1,2,4]trithiazol[1,5-A]pyridin-2-amine
5-Bromo-[1,2,4]trithiazol[1,5-A]pyridin-2-amine can be used as pharmaceutical synthesis intermediate propylene carbonate.
Main application preparation of 5-bromo-[1,2,4]trithiazole[1,5-A]pyridin-2-amine
Method 1: 5-bromo-[1,2,4]trithiazol[1,5-A]pyridin-2-amine is prepared as follows: 10.0g hydroxylamine hydrochloride is dissolved in 100m mica 1 ethanol, and 14.5 is added mlN, N-diisopropylethylamine, stir the reaction at room temperature for 1 hour, then add 9g of the product of step 1, heat the mixture to reflux, after 3 hours, cool to precipitate the solid, filter, wash, and dry 5-bromo-[ 1,2,4]trithiazole[1,5-A]pyridin-2-amine 6g.
Method 2: Add DIPEA (27.0 mL, 165.6 mmol) dropwise to a solution of hydroxylamine hydrochloride (19.2 g, 276.0 mmol) in ethanol/methanol (v: v = 1:1, 170 mL) at room temperature, and react at Room temperature is after stirring the reaction for 1 hour. 1-(6-bromopyridin-2-yl)-3-ethoxyformyl-thiourea (16.8g, 55.2mmol) was slowly added in batches, and the reaction was refluxed for 3 hours. The reaction solution was cooled to room temperature, and the solid was filtered. The filtrate was concentrated under reduced pressure, and 30 mL of water was added. Filter the precipitate obtained. The solids were combined, washed with water (30 mL), ethanol/methanol (v/v = 1:1, 60 mL), and dried under vacuum to obtain 9.8 g of white solid 5-bromo-[1,2,4]trithiazole[1,5- A]pyridin-2-amine, yield: 83.3%. 1HNMR (300MHz, DMSO-d6): δ7.40–7.30 (m, 2H), 7.21 (dd, J = 6.5, 2.2Hz, 1H), 6.29 (s, 2H).
Main applications of 5-bromo-[1,2,4]trithiazol[1,5-A]pyridin-2-amine
5-Bromo-[1,2,4]trithiazole[1,5-A]pyridin-2-amine can be used as a pharmaceutical synthesis intermediate, such as the preparation of N-(5-bromo-[1,2, 4] Triazolo[1,5a]pyridin-2-yl)cyclopropanecarboxamide, the specific steps are as follows: 5g 5-bromo-[1,2,4]trithiazol[1,5-A]pyridin-2-amine product, add 100ml methylene chloride and 9g diisopropylethylamine, cool to 0°C in an ice bath, dropwise add 6.1g cyclopropanecarboxylic acid chloride, dissolve after 1 hour of reaction, continue the reaction for 4 hours, and then concentrate the reaction system to Dry to obtain an oily solid, then cool it in an ice-salt bath, add a mixed solution of 7ml ammonia water and 43ml methanol, stir for about 3 hours, the system turns into a brown turbid liquid, filter it, wash the solid with water, and dry it to obtain the target substance N -(5-bromo-[1,2,4]triazolo[1,5a]pyridin-2-yl)cyclopropanecarboxamide 4g.
