Phosphorus oxychloride → HCID 71470277, compound

Temperature

-25 °C

L-Boc-Lys(Boc)-OH (0.26 g, 0.75 mmol) was dissolved in 3 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., 3-((perfluoropyridin-4-yl)ethynyl)aniline, (13b) (0.10 g, 0.36 mmol) in pyridine (3 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 Na SO4 and was concentrated in vacuo. The crude product was subjected to chromatography with CH2Cl2:CH3CN=1:30 and the product was obtained in 36% yield. (S)-Di-tert-butyl (6-oxo-6-((3-((perfluoropyridin-4-yl)ethynyl)phenyl)amino)hexane-1,5-diyl)dicarbamate (97 mg, 0.16 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 solvent was evaporated and the product (65 mg, 86%) was purified by recrystallization with isopropanol: 1H-NMR (600 MHz, CD3OD) δ 8.07 (dd, J=1.74 Hz, J=1.68 Hz, 1H), 7.75 (ddd, J=7.98 Hz, J=1.92 Hz, J=1.14 Hz, 1H), 7.48 (dd, J=7.8 Hz, J=7.8 Hz, 1H), 7.43 (ddd, J=7.68 Hz, J=1.32 Hz, J=1.32 Hz, 1H) 4.12 (t, J=6.6 Hz, 1H), 2.97 (t, J=7.56 Hz, 2H), 2.00-2.07 (m, 1H), 1.97-2.00 (m, 1H), 1.74-1.77 (m, 2H), 1.56-1.60 (m, 2H); 13C-NMR (150 MHz, CD3OD) δ 168.7, 144.9 (dm, J=224 Hz), 143.5 (dm, J=262 Hz), 139.7, 130.8, 129.4, 124.2, 123.3, 122.4, 117.9 (m), 106.5 (m), 74.2 (m), 54.9, 40.3, 32.2, 28.2, 23.0; m.p. >250° C. (decomp.)

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 Na SO4
7. concentrationwas concentrated in vacuo
8. customCH3CN=1:30 and the product was obtained in 36% yield
9. stirringthe solution was stirred for 10 hours at room temperature
10. customThe solvent was evaporated
11. customthe product (65 mg, 86%) was purified by recrystallization with isopropanol

ORD record

ord-26bc57632e0a4c64b3839eb399803bf2

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08927728B2