Reacción #89477

Ecuación de reacción

2-fluoro-6-(pyrimidin-2-yl)benzoic acid

2-chloro-4,6-dimethoxy-1,3,5-triazine

N-methylmorpholine

2-(((2S,3R)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione

→

title compound

Rendimiento 15.5%

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

Rendimiento 15.5%

Disolventes

EtOAc

1,4-dioxane

1,4-dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONAfter the addition
2. 2
   TemperaturaThe reaction mixture was cooled to rt
3. 3
   Lavadosubsequently washed with 0.1 N HCl (100 mL), 0.1 N NaOH (100 mL), and brine (100 mL)
4. 4
   Secadodried over Na2SO4
5. 5
   Filtraciónfiltered
6. 6
   Concentraciónconcentrated under reduced pressure
7. 7
   OtroThe residue was purified by flash column chromatography on silica gel (0% to 100% EtOAc/hexanes)

Procedimiento

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.

Fuente