Tetrahydrofuran → N-[4-(4-nitrophenoxy)-2-pyridinyl]-4-morpholinecarboxamide

4-(4-Nitrophenoxy)pyridin-2-ylamine (100 mg) was dissolved in tetrahydrofuran (5 ml) under a nitrogen atmosphere, and triethylamine (0.181 ml) and phenyl chloroformate (0.163 ml) were added while stirring and cooling in an ice water bath. The reaction mixture was allowed to warm up to room temperature, followed by stirring for 30 min. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (30 ml). The separated organic layer was washed with water (30 ml) and brine (30 ml) in this order, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue was added N,N-dimethylformamide (5 ml), then morpholine (0.189 ml) was added, followed by stirring for 3 hr. The reaction mixture was concentrated under reduced pressure, and the resultant residue was partitioned after addition of ethyl acetate (50 ml) and a saturated aqueous solution of ammonium chloride (30 ml). The separated organic layer was washed with a saturated aqueous solution of ammonium chloride (30 ml), water (30 ml) and brine (30 ml), and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=1:3, then ethyl acetate). Fractions containing the target compound were concentrated under reduced pressure to provide roughly-purified titled compound as a pale yellow solid (128.8 mg).

1. temperaturecooling in an ice water bath
2. stirringby stirring for 30 min
3. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
4. washThe separated organic layer was washed with water (30 ml) and brine (30 ml) in this order
5. dry with materialdried over anhydrous sodium sulfate
6. customThe solvent was removed under reduced pressure
7. additionTo the residue was added N,N-dimethylformamide (5 ml)
8. additionmorpholine (0.189 ml) was added
9. stirringby stirring for 3 hr
10. concentrationThe reaction mixture was concentrated under reduced pressure
11. customthe resultant residue was partitioned
12. additionafter addition of ethyl acetate (50 ml)
13. washThe separated organic layer was washed with a saturated aqueous solution of ammonium chloride (30 ml), water (30 ml) and brine (30 ml)
14. dry with materialdried over anhydrous sodium sulfate
15. customThe solvent was removed under reduced pressure
16. customthe residue was purified by silica gel column chromatography (eluent
17. additionFractions containing the target compound
18. concentrationwere concentrated under reduced pressure
19. customto provide
20. customroughly-purified titled compound as a pale yellow solid (128.8 mg)

ORD record

ord-4ce78862598b4e76a6c2b69a22023dfe

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07855290B2