反应详情

A solution of 120 mg (0.336 mmol) of 7-[(2,3-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid from Example 117A in 2 ml of DMF was admixed with 70.8 mg (0.437 mmol) of 1,1′-carbonyldiimidazole and 36 mg (0.235 mmol) of 1-hydroxybenzotriazole. After stirring at room temperature for 15 min, 94.4 mg (0.437 mmol) of rac-(1-amino-2-methylpentan-2-yl)carbamic acid tert-butyl ester from Example 152A were added, followed by 0.117 ml (0.672 mmol) of N,N-diisopropylethylamine. The tubes were sealed and introduced into a Biotage Initiator with microwave irradiation at 100° C. for 20 minutes. The reaction mixture was partitioned between ethyl acetate (10 ml) and water (10 ml), the phases were separated and the aqueous phase was acidified to pH=5 with 2 N aqueous hydrochloric acid and extracted with dichloromethane (2×15 ml). The combined organic phases were concentrated under reduced pressure and the residue was purified by flash chromatography using a prepacked silica gel cartridge (eluent:cyclohexane-ethyl acetate 10:1 to 1:1), which gave 35 mg (15% of theory, 78% pure) of the target compound.

1. customThe tubes were sealed
2. additionintroduced into a Biotage Initiator with microwave irradiation at 100° C. for 20 minutes
3. customThe reaction mixture was partitioned between ethyl acetate (10 ml) and water (10 ml)
4. customthe phases were separated
5. extractionextracted with dichloromethane (2×15 ml)
6. concentrationThe combined organic phases were concentrated under reduced pressure
7. customthe residue was purified by flash chromatography
8. customgave 35 mg (15% of theory, 78% pure) of the target compound