Methyl iodide → HCID 86696528, compound

Temperature

0 °C

To a solution of trans-2-chloro-N-((2-(4-fluorophenyl)cyclopropyl)methyl)-3-(trifluoromethyl)pyridin-4-amine (1.2 g, 3.48 mmol) in DMF (5 mL) was added 60% sodium hydride in mineral oil (0.153 g, 3.83 mmol) at 0° C. The resulting mixture was stirred at 0° C. under nitrogen for 10 min. Iodomethane (0.022 mL, 0.346 mmol) was added at 0° C. The reaction mixture was stirred at 0° C. for 10 min and then at rt for 30 min. The reaction mixture was poured into ice water and the resulting suspension was extracted with EtOAc (3×20 mL). The combined organic layers were washed with aqueous sodium bicarbonate (2×20 mL) and brine (20 mL), dried over magnesium sulfate, filtered and concentrated under vacuum to give trans-2-chloro-N-((2-(4-fluorophenyl)cyclopropyl)methyl)-N-methyl-3-(trifluoromethyl)pyridin-4-amine (1.2 g, 96% yield) as a yellowish oil, which was used for the next step reaction without further purification. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.07 (d, J=5.8 Hz, 1H), 7.01-6.94 (m, 4H), 6.80 (d, J=6.0 Hz, 1H), 3.38 (dd, J=14.1, 6.0 Hz, 1H), 3.18 (dd, J=14.1, 7.3 Hz, 1H), 3.06-3.00 (m, 3H), 1.75-1.63 (m, 1H), 1.24 (br. s., 1H), 1.03 (dt, J=8.5, 5.3 Hz, 1H), 0.90-0.84 (m, 1H). LCMS: M+1=359.17.

1. stirringThe reaction mixture was stirred at 0° C. for 10 min
2. waitat rt for 30 min
3. extractionthe resulting suspension was extracted with EtOAc (3×20 mL)
4. washThe combined organic layers were washed with aqueous sodium bicarbonate (2×20 mL) and brine (20 mL)
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated under vacuum

ORD record

ord-cd70ce84a34e4881895a3f12ae687f51

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765767B2