Methanesulfonic Acid → HCID 178432597、化合物

To a solution of 4-cyanopyridine N-oxide (100 mg) in methanol (4 mL) were added sodium methoxide (13.5 mg), and the mixture was stirred at room temperature for 24 hrs. To the reaction mixture was added methanesulfonic acid (104 mg), and the reaction mixture was stirred at room temperature for an additional 10 minutes. To the 3.5 ml of this solution was added to the solution (2 mL) of (2S)-1-(4-fluorophenyl)-1-(6-fluoro-3-pyridyl)-1,2-propanediamine described in Reference Example 5-1, and the mixture was stirred at room temperature for 15 hrs. After concentrating the reaction mixture in vacuo, the obtained residue was dissolved in ethyl acetate, washed with saturated sodium hydrogen carbonate aqueous solution and saturated sodium chloride aqueous solution in this order, and dried over anhydrous sodium sulfate. Sodium sulfate was removed by filtration, and the organic solvent was evaporated in vacuo. The obtained residue was purified by silica gel column chromatography (C-300; chloroform: methanol=9:1) to give 2-(1-oxido-pyridin-4-yl)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5-methyl-2-imidazoline (172 mg) as colorless oil. To the solution (5 ml) of the obtained N-oxide compound in acetonitrile was added trimethylsilylcyanide (140 mg) and triethylamine (142 mg), and the mixture was stirred at 90° C. for 17 hrs. To the mixture was added trimethylsilylcyanide (140 mg) and triethylamine (142 mg), and the mixture was stirred at 90° C. for 2 hrs, and concentrated in vacuo. The obtained residue was dissolved in chloroform, washed with saturated sodium hydrogen carbonate aqueous solution, water and saturated sodium chloride aqueous solution in this order, and dried over anhydrous sodium sulfate. Sodium sulfate was removed by filtration, and the organic solvent was evaporated in vacuo. The obtained residue was purified by silica gel column chromatography (C-300; hexane: ethyl acetate=1:1) and treated with 4N hydrogen chloride—ethyl acetate solution to give the title compound (108 mg).

1. stirringthe reaction mixture was stirred at room temperature for an additional 10 minutes
2. stirringthe mixture was stirred at room temperature for 15 hrs
3. concentrationAfter concentrating the reaction mixture in vacuo
4. dissolutionthe obtained residue was dissolved in ethyl acetate
5. washwashed with saturated sodium hydrogen carbonate aqueous solution and saturated sodium chloride aqueous solution in this order
6. dry with materialdried over anhydrous sodium sulfate
7. customSodium sulfate was removed by filtration
8. customthe organic solvent was evaporated in vacuo
9. customThe obtained residue was purified by silica gel column chromatography (C-300; chloroform: methanol=9:1)

ORDレコード

ord-0aafa56aaaa74a32968442ea122bbc48

出典データセット

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07482358B2