2-Cyano-4-ethoxycarbonylpyrimidine → HCID 178469215, compound

Participants

Reaction Conditions

Reaction Steps

2-Cyano-4-ethoxycarbonylpyrimidine (207.3 mg) and scandium trifluoromethanesulfonate (48.8 mg) were added to a solution of (2R)-1,1-bis(4-fluorophenyl)-3-methoxymethoxy-1,2-propanediamine (303.5 mg) in toluene (2.0 mL), and the mixture was stirred at 110° C. for 4 hours. The reaction mixture was concentrated in vacuo, and then the residue was purified by silica gel column chromatography (C-300; hexane:ethyl acetate=1:1→1:2) to give (5R)-2-(4-ethoxycarbonyl-2-pyrimidyl)-4,4-bis(4-fluorophenyl)-5-[(methoxymethoxy)methyl]-2-imidazoline (279 mg). The obtained ester compound was dissolved in methanol (2 mL), and ammonia gas was passed through the solution at −78° C. for 20 minutes. Then the solution was stirred at room temperature for 20 hours. The reaction mixture was concentrated in vacuo, and then the residue was purified by silica gel column chromatography (C-300; hexane:ethyl acetate=1:1→chloroform:methanol=9:1) to give the corresponding amide compound (273 mg). Triethylamine (0.75 mL) and trifluoroacetic anhydride (0.26 mL) were added at −78° C. to a solution of the obtained amide compound in tetrahydrofuran (2 mL), and the temperature of the mixture was raised up to room temperature, followed by stirring for 7 hours. Water was added to the reaction mixture, and the mixture was extracted by ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and then sodium sulfate was removed by filtration. Then the organic solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography (C-300; hexane:ethyl acetate=1:1→1:2) to give the corresponding cyano compound (178 mg). The obtained cyano compound was dissolved in tetrahydrofuran (6 mL), and 6N hydrochloric acid(6 mL) was added to the solution. Then the mixture was stirred at room temperature for 5 hours. Saturated sodium hydrogen carbonate aqueous solution was added to the reaction mixture carefully, and the mixture was extracted by ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and then sodium sulfate was removed by filtration. The organic solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography (C-300; chloroform:ethyl acetate=2:1) to give the title compound (74.7 mg).

Provenance & Evidence