反应详情

To a solution of tert-butyl 3-(4-((4-((3S)-3-cyano-3-cyclopropyl-2-oxopyrrolidin-1-yl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)azetidine-1-carboxylate (300 mg) obtained in Step C of Example 131 in ethyl acetate (5 mL) was added a solution of 4 M hydrogen chloride in ethyl acetate (10 mL), and the mixture was stirred at room temperature for 30 min. The solvent was evaporated under reduced pressure, to a suspension of the reaction mixture in tetrahydrofuran (10 mL) were added triethylamine (1.3 g) and methoxyacetyl chloride (77 mg) at room temperature, and the mixture was stirred at room temperature for 3 hr. The solvent was evaporated under reduced pressure, and the reaction mixture was poured into water, and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/methanol). The obtained crude product was subjected to HPLC (C18, mobile phase: water/acetonitrile (containing 10 mM NH4HCO3)), and the obtained fraction was concentrated under reduced pressure. The residue was recrystallized (ethyl acetate/diisopropyl ether) to give the title compound (60 mg).

1. customThe solvent was evaporated under reduced pressure, to a suspension of the reaction mixture in tetrahydrofuran (10 mL)
2. additionwere added triethylamine (1.3 g) and methoxyacetyl chloride (77 mg) at room temperature
3. stirringthe mixture was stirred at room temperature for 3 hr
4. customThe solvent was evaporated under reduced pressure
5. additionthe reaction mixture was poured into water
6. extractionextracted with ethyl acetate
7. washThe obtained organic layer was washed with saturated brine
8. dry with materialdried over anhydrous magnesium sulfate
9. customthe solvent was evaporated under reduced pressure
10. customThe residue was purified by silica gel column chromatography (NH, ethyl acetate/methanol)
11. customThe obtained crude product
12. concentrationthe obtained fraction was concentrated under reduced pressure
13. customThe residue was recrystallized (ethyl acetate/diisopropyl ether)