反应详情

The mixture of 1-cyclobutyl-1H-indazole-3-carboxylic acid (135 mg, 0.63 mmol, step 2 of Example 4), tert-butyl cis-5-amino-2-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidine-1-carboxylate (197 mg, 6.27 mmol, step 5 of Example 2), diethyl cyanophosphonate (0.13 mL, 0.75 mmol), and N,N-diisopropylethylamine (0.16 mL, 0.94 mmol) in N,N-dimethylformamide (10 mL) was stirred at room temperature for 12 h. Then the mixture was poured onto aqueous saturated sodium hydrogencarbonate (100 mL), and the aqueous layer was extracted with ethyl acetate/toluene (3:1, 100 mL×3). The combined organic layer was concentrated under reduced pressure. The residue was chromatographed on a column of silica gel eluting with ethyl acetate/n-hexane (1:2) to give 112 mg (35%) of the title compound as a pale yellow amorphous.

1. extractionthe aqueous layer was extracted with ethyl acetate/toluene (3:1, 100 mL×3)
2. concentrationThe combined organic layer was concentrated under reduced pressure
3. customThe residue was chromatographed on a column of silica gel eluting with ethyl acetate/n-hexane (1:2)