N-[5-[4-[(1,1-dioxo-4-thiomorpholinyl)methyl]phenyl][1,2,4]triazolo[1,5-A]pyridine -2-yl]cyclopropanecarboxamide_Kain Industrial Additive

Background and overview^[1]

N-[5-[4-[(1,1-dioxo-4-thiomorpholinyl)methyl]phenyl][1,2,4]triazolo[1,5- A]pyridin-2-yl]cyclopropanecarboxamide can be used as a pharmaceutical synthesis intermediate.

Preparation^[1]

N-[5-[4-[(1,1-dioxo-4-thiomorpholinyl)methyl]phenyl][1,2,4]triazolo[1,5- Preparation of A]pyridin-2-yl]cyclopropanecarboxamide (8A): 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane- 2-yl)-benzyl)thiomorpholine 1,1-dioxide (Intermediate 1A) (20.18g, 53mmol), N-(5-bromo-[1,2,4]triazolo[1 ,5-a]pyridin-2-yl)cyclopropanecarboxamide (Intermediate 7A) (16.45g, 59mmol), Pd(dppf)Cl2 (3.91g, 5mmol), K2CO3 (22.06g, 160mmol) were added to 250mL in sequence into a three-necked flask, then add 1,4-dioxane (100 mL) and water (25 mL), and raise the temperature to 90°C under argon protection for 12 hours. After the reaction is completed, cool to room temperature, add 300 mL of methylene chloride to the reaction solution, and then wash with water twice, 500 mL each time. The organic phase is dried over anhydrous sodium sulfate, and the organic phase is concentrated to dryness. The residue is passed through column chromatography. (Eluent: dichloromethane: methanol = 50:1) Purification, the title product N-[5-[4-[(1,1-dioxo-4-thiomorpholinyl)methyl]benzene is obtained [1,2,4]triazolo[1,5-A]pyridin-2-yl]cyclopropanecarboxamide, 11g of light yellow solid.

Apply^[1]

N-[5-[4-[(1,1-dioxo-4-thiomorpholinyl)methyl]phenyl][1,2,4]triazolo[1,5- A]pyridin-2-yl]cyclopropanecarboxamide can be used as a pharmaceutical synthesis intermediate, if the following reaction occurs:

N-[5-[4-[(1,1-dioxo-4-thiomorpholinyl)methyl]phenyl][1,2,4]triazolo[1,5 -A]pyridin-2-yl]cyclopropanecarboxamide (1.00g, 2.4mmol) was added to a 50mL single-neck bottle, and 20mL of toluene and Lawson’s reagent (0.48g, 1.2mmol) were added in sequence. Under argon protection, the mixture was refluxed for 7 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered with suction, and the filtrate was concentrated to dryness under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane: methanol = 50:1) to obtain the title product as a yellow solid 0.8 g.

Main reference materials

[1] (CN107759587)[1,2,4]triazolo[1,5‑a]pyridine compounds and their preparation methods and medicinal uses