4-Methylmorpholine → 2-(((2S,3R)-1-(2-Fluoro-6-(pyrimidin-2-yl)benzoyl)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione

Temperature

80 °C

A solution of 2-fluoro-6-(pyrimidin-2-yl)benzoic acid (366 mg, 1.67 mmol), 2-chloro-4,6-dimethoxy-1,3,5-triazine (292 mg, 1.67 mmol), and N-methylmorpholine (421 mg, 4.18 mmol) in anhydrous 1,4-dioxane (10 mL) was stirred at rt under nitrogen for 1.5 h. A solution of 2-(((2S,3R)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione (359 mg, 1.39 mmol) in anhydrous 1,4-dioxane (3 mL) was added at rt. After the addition was completed, the reaction was heated to 80° C. under nitrogen for 5 h. The reaction mixture was cooled to rt, diluted with EtOAc (100 mL), subsequently washed with 0.1 N HCl (100 mL), 0.1 N NaOH (100 mL), and brine (100 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (0% to 100% EtOAc/hexanes) to afford the title compound as a white foam (99 mg, 15%). ESI MS (M+H) 459.

1. additionAfter the addition
2. temperatureThe reaction mixture was cooled to rt
3. washsubsequently washed with 0.1 N HCl (100 mL), 0.1 N NaOH (100 mL), and brine (100 mL)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by flash column chromatography on silica gel (0% to 100% EtOAc/hexanes)

ORD record

ord-459f3c8d67f74102a9567f7f3da642cd

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09440982B2