Iodoethane → 2-ethyl-4-nitro-2H-1,2,3-triazole

To a solution of 4-nitro-2H-1,2,3-triazole (2.02 g, 17.7 mmol) in N,N-dimethylformamide (40 ml), sodium hydride (1.06 g, 26.6 mmol) was added at 0° C., and the mixture was stirred at room temperature for 10 minutes. To the reaction solution was added ethyl iodide (4.15 g, 26.6 mmol), followed by stirring the mixture overnight at room temperature. To the reaction solution was added a saturated aqueous sodium bicarbonate solution, the mixture was then extracted with ethyl acetate, and the combined organic layers were washed with water and a saturated saline solution, then dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (Biotage, hexane:ethyl acetate=5:1 to 1:4) to give 2-ethyl-4-nitro-2H-1,2,3-triazole (1.35 g, yield: 53%) as a pale yellow oily substance. 2) To a solution of nitro intermediate (1.35 g, 9.46 mmol), obtained in the above reaction, in methanol (30 ml), was added palladium carbon (500 mg, 50% wet, 4.70 mmol), followed by overnight stirring the mixture under hydrogen atmosphere at room temperature under a pressure of one atmosphere. The reaction solution was filtered through Celite to remove palladium carbon, and the solvent was concentrated under reduced pressure to give 2-ethyl-2H-1,2,3-triazol-4-amine (979 mg, yield: 92%) as a red oily substance. 3) Using 2-ethyl-2H-1,2,3-triazol-4-amine (979 mg, 8.73 mmol) obtained in the above reaction and 4-chloroquinazolin-6-ylacetate (1.94 g, 8.73 mmol), 4-[(2-ethyl-2H-1,2,3-triazol-4-yl)amino]quinazolin-6-ol (1.52 g, yield: 68%) was obtained as a gray solid by the method as in Example 76.

1. stirringby stirring the mixture overnight at room temperature
2. extractionthe mixture was then extracted with ethyl acetate
3. washthe combined organic layers were washed with water
4. dry with materiala saturated saline solution, then dried over anhydrous sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe resultant residue was purified by silica gel column chromatography (Biotage, hexane:ethyl acetate=5:1 to 1:4)

ORD record

ord-38b216ce7cad457a9f475fa2d51c4d3d

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846700B2