Phosphorus oxychloride → HCID 71470274, compound

Temperature

-25 °C

L-Boc-Orn(Boc)-OH (0.25 g, 0.75 mmol) was dissolved in 1.5 mL of pyridine. The solution was cooled to −25° C. and phosphorus oxychloride (0.12 g, 0.75 mmol) was added dropwise with vigorous stirring. After stirring for 15 min. at −25° C., 4-((perfluoropyridin-4-yl)ethynyl)aniline, (13a) (0.10 g, 0.38 mmol) in pyridine (1.5 mL) was added slowly. The reaction mixture was stirred for 0.5 h at −25° C. and then at room temperature for 10 h. The reaction mixture was quenched with ice/water and extracted with EtOAc. The organic layer was washed with sat. NaHSO4 three times, dried with Na2SO4 and was concentrated in vacuo. The crude product was subjected to chromatography with MeOH:CH2Cl2=1:80 and the Boc-protected product was obtained in 23% yield. (S)-Di-tert-butyl (5-oxo-5-((4-((perfluoropyridin-4-yl)ethynyl)phenyl)amino)pentane-1,4-diyl)dicarbamate (100 mg, 0.17 mmol) was dissolved in gaseous HCl saturated MeOH (4 mL) at 0° C. and the solution was stirred for 10 hours at room temperature. The precipitated product (40 mg, 51%) was obtained by filtration: 1H-NMR (300 MHz, CD3OD) δ 7.82 (d, J=9.0 Hz, 2H), 7.65 (d, J=8.7 Hz, 2H), 4.15 (t, J=6.3 Hz, 1H), 3.14 (t, J=8.4 Hz, 2H), 2.02-2.09 (m, 2H), 1.83-1.88 (m, 2H)

1. stirringThe reaction mixture was stirred for 0.5 h at −25° C.
2. waitat room temperature for 10 h
3. customThe reaction mixture was quenched with ice/water
4. extractionextracted with EtOAc
5. washThe organic layer was washed with sat. NaHSO4 three times
6. dry with materialdried with Na2SO4
7. concentrationwas concentrated in vacuo
8. customwas obtained in 23% yield
9. stirringthe solution was stirred for 10 hours at room temperature

ORD record

ord-c6edf8a804bb43ef9ce86c7461ee3ecd

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08927728B2