2-Methoxyethylamine → 4-(4-chloro-2-fluorophenyl)-N-(2-methoxyethyl)-2-methylnicotinamide

Temperature

70 °C

A solution of 4-(4-chloro-2-fluorophenyl)-2-methylnicotinic acid (2 g, 5.19 mmol), prepared as described in Example 16, Part E, in thionyl chloride (5 mL, 68.5 mmol) was heated at 70° C. for 2 h. After cooling, the volatiles were removed under reduced pressure. The residue was dissolved in 4 mL of anhydrous DCM and added to a pre-cooled solution of 2-methoxyethanamine (0.390 g, 5.19 mmol) and triethyl amine (3.62 mL, 26.0 mmol) in DCM (8 mL) at 0° C. The resulting reaction mixture was stirred at rt for 4 h. Water (30 mL) was then added and the solution was extracted with DCM (2×20 mL). The combined organic layers were washed with brine (20 mL), dried over sodium sulphate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography using a gradient of EtOAc and hexane as eluant to yield 4-(4-chloro-2-fluorophenyl)-N-(2-methoxyethyl)-2-methylnicotinamide (1.3 g, 2.88 mmol, 56% yield) as a yellow oil. LC/MS (ESI) m/e 323.1 [(M+H)+, calcd for C16H17ClFN2O2 323.1]; LC/MS retention time (method D): tR=0.61 min.

1. temperatureAfter cooling
2. customthe volatiles were removed under reduced pressure
3. dissolutionThe residue was dissolved in 4 mL of anhydrous DCM
4. customThe resulting reaction mixture
5. extractionthe solution was extracted with DCM (2×20 mL)
6. washThe combined organic layers were washed with brine (20 mL)
7. dry with materialdried over sodium sulphate
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel chromatography

ORD record

ord-de5dbbc31cd94096b4f236d1f3afb1aa

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901305B2