Sodium Iodide → 6-(((2S,4R)-1-acetyl-6-(2-(2-methoxyethyl)-2H-1,2,3-triazol-4-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

Participants

Reaction Conditions

Reaction Steps

A solution of 6-(((2S,4R)-1-acetyl-2-methyl-6-(1H-1,2,3-triazol-4-yl)-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (for a preparation see Intermediate 8) (50 mg, 0.134 mmol) in DMF (3 ml) was cooled to 0° C. in an ice-water bath. To the solution was added 1-bromo-2-methoxyethane (0.04 ml, 0.420 mmol) and potassium carbonate (56 mg, 0.405 mmol). The solution was then allowed to warm to room temperature, and was stirred at ambient conditions for 2 h. Sodium iodide (61 mg, 0.407 mmol) was added to the reaction solution and the reaction was stirred at ambient temperature overnight. 1-Bromo-2-methoxyethane (0.013 ml, 0.134 mmol), potassium carbonate (21 mg, 0.152 mmol), and sodium iodide (21 mg, 0.140 mmol) were added to the reaction, which was heated at 60° C. for 1 h. Further portions of 1-bromo-2-methoxyethane (0.013 ml, 0.134 mmol), potassium carbonate (21 mg, 0.152 mmol), and sodium iodide (21 mg, 0.140 mmol) were added to the reaction and heating continued for 3 h. The reaction mixture was concentrated in vacuo, diluted with water (10 ml) and extracted with DCM (3×15 ml). The organics were combined and dried (hydrophobic frit). The solvent was then evaporated in vacuo, the sample redissolved in methanol/DMSO (1:1, 1 ml) and purified by MDAP (formate). Both regiosiomers were collected to give 6-(((2S,4R)-1-acetyl-6-(1-(2-methoxyethyl)-1H-1,2,3-triazol-4-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (8 mg) and 6-(((2S,4R)-1-acetyl-6-(2-(2-methoxyethyl)-2H-1,2,3-triazol-4-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4- yl)amino)nicotinonitrile (18 mg).

Provenance & Evidence