Sodium Hydroxide → 4-(1-Methyl-azetidin-3-yl)piperazine-1-carboxylic acid [4-(2-fluoro-4nitrophenoxy)pyridin-2-yl]amide

To a solution of 4-(2-fluoro-4-nitrophenoxy)pyridin-2-ylamine (70.0 mg) in tetrahydrofuran (3.5 ml) were added triethylamine (0.0862 ml) and phenyl chloroformate (0.0705 ml) in this order at room temperature, followed by stirring at room temperature for 30 min. The reaction mixture was concentrated to give a residue, to which were added N,N-dimethylformamide (2.5 ml), triethylamine (0.470 ml), 1-(1-methylazetidin-3-yl)piperazine trihydrochloride (329 mg) and water (0.025 ml), followed by stirring at room temperature for 2 days. An 1N aqueous solution of sodium hydroxide (30 ml) was added thereto, followed by stirring at room temperature for 5 hrs. The reaction mixture was extracted with ethyl acetate (100 ml). The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, and dried over anhydrous sodium sulfate. The organic layer was concentrated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=20:1). Fractions containing the target compound were concentrated to provide the titled compound (121 mg, 92.6%) as a pale yellow oil.

1. concentrationThe reaction mixture was concentrated
2. customto give a residue
3. stirringby stirring at room temperature for 2 days
4. stirringby stirring at room temperature for 5 hrs
5. extractionThe reaction mixture was extracted with ethyl acetate (100 ml)
6. extractionThe aqueous layer was extracted with ethyl acetate
7. washThe combined organic layer was washed with brine
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationThe organic layer was concentrated
10. customto give a residue, which
11. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent
12. additionFractions containing the target compound
13. concentrationwere concentrated

ORDレコード

ord-f9b2fc507c5441f8a9d7bbd0b187e860

出典データセット

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07531532B2