Benzenamine, 3-(methylthio)- → Methyl 6-chloro-4-cyano-2-(3-(methylthio)phenylamino)nicotinate

Temperature

60 °C

A mixture of methyl 2,6-dichloro-4-cyanonicotinate (340.8 mg, 1.475 mmol), DIPEA (0.3 mL, 1.718 mmol) and 3-(methylthio)aniline (234.8 mg, 1.687 mmol) in CH3CN (5 mL) was stirred at 60° C. for 2 days. After the mixture was cooled, saturated aq NaHCO3 (30 mL) was added and the mixture was extracted with EtOAc (2×30 mL). The organic layers were washed with saturated aq NaHCO3 (20 mL), water (20 mL) and brine (20 mL), were dried over anhydrous Na2SO4, and then filtered through SiO2. The filtrate was concentrated under reduced pressure and the residue was washed with IPE and filtered to give the title compound as a yellow solid (157.8 mg). The filtrate was purified by column chromatography (SiO2, hexanes/EtOAc=8/1) to give another crop (135.5 mg) of the title compound as a yellow oil of (total 293 mg, 60%). 1H-NMR (CDCl3) δ ppm 2.52 (s, 3H), 4.05 (s, 3H), 7.00 (s, 1H), 7.03-7.05 (m, 1H), 7.25-7.32 (m, 2H), 7.66-7.67 (m, 1H), 10.51 (br s, 1H). [M+H] calc'd for C15H13ClN3O2S, 334; found, 334.

1. temperatureAfter the mixture was cooled
2. extractionthe mixture was extracted with EtOAc (2×30 mL)
3. washThe organic layers were washed with saturated aq NaHCO3 (20 mL), water (20 mL) and brine (20 mL)
4. dry with materialwere dried over anhydrous Na2SO4
5. filtrationfiltered through SiO2
6. concentrationThe filtrate was concentrated under reduced pressure
7. washthe residue was washed with IPE
8. filtrationfiltered

ORD record

ord-68e09bbec4284d038bb0aa26dd37a583

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09108970B2