反应详情

A solution of 176 mg (0.75 mmol) of product 1 (methyl (3-oxo-2,3,4,5-tetrahydro-1-H-2-benzazepin-4-yl)carbamate, which can be prepared according to WO 02/057257 and the content of the description of which is incorporated herein by reference), dissolved in a mixture of 2 ml of dry THF and 2 ml of dry DMF is added dropwise at room temperature to a suspension of 36 mg (0.9 mmol) of 60% NaH dispersed in oil, suspended in 2 ml of anhydrous THF, under an inert atmosphere. At the end of the addition, 159 mg (1.5 eq.) of methyl iodide are added. The reaction mixture is then stirred at room temperature for 2 hours, and 10 ml of saturated ammonium chloride solution are then added, while cooling the reaction medium in an ice bath. The mixture is extracted with 3×10 ml of ethyl acetate. The organic phases are combined, washed with 2×10 ml of saturated NaCl solution, dried over magnesium sulfate and evaporated to dryness under reduced pressure. The oily residue obtained is chromatographed on silica gel, eluting with a 90/10 dichloromethane/methanol mixture. 82 mg (44%) of the expected product 2 are obtained in the form of an oil.

1. additiondispersed in oil
2. additionare added
3. temperaturewhile cooling the reaction medium in an ice bath
4. extractionThe mixture is extracted with 3×10 ml of ethyl acetate
5. washwashed with 2×10 ml of saturated NaCl solution
6. dry with materialdried over magnesium sulfate
7. customevaporated to dryness under reduced pressure
8. customThe oily residue obtained
9. customis chromatographed on silica gel
10. washeluting with a 90/10 dichloromethane/methanol mixture