反应详情

A solution of 170 mg (0.366 mmol, 75% purity) of 7-[(2,6-difluorobenzyl)oxy]-5-methoxy-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic acid (Example 163A) in 8 ml of tetrahydrofuran was admixed with 84 mg (0.44 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS: 25952-53-8) and 60 mg (0.44 mmol) of 1-hydroxy-7-azabenzotriazole (CAS: 39968-33-7). The solution was stirred at room temperature for 20 minutes. The reaction mixture was admixed with 0.191 ml (1.01 mmol) of N,N-diisopropylethylamine and 158 mg (0.732 mmol) of rac-(1-amino-2-methylpentan-2-yl)carbamic acid tert-butyl ester (Example 152A). The mixture was stirred at room temperature for a further 18 hours, and the reaction mixture was then concentrated under reduced pressure. The residue was partitioned between dichloromethane and water. The organic phase was removed, extracted with a saturated aqueous sodium hydrogencarbonate solution, water and aqueous sodium chloride solution, dried over sodium sulphate, filtered and concentrated under reduced pressure. The remaining residue was purified by flash chromatography using a prepacked silica gel cartridge (eluent:dichloromethane/methanol, gradient 0% to 10%), which gave 120 mg (44% yield, 73% purity) of product.

1. stirringThe mixture was stirred at room temperature for a further 18 hours
2. concentrationthe reaction mixture was then concentrated under reduced pressure
3. customThe residue was partitioned between dichloromethane and water
4. customThe organic phase was removed
5. extractionextracted with a saturated aqueous sodium hydrogencarbonate solution, water and aqueous sodium chloride solution
6. dry with materialdried over sodium sulphate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe remaining residue was purified by flash chromatography
10. customgave 120 mg (44% yield, 73% purity) of product