Ethyl Acetate → 4-[2-chloro-4-({5-[2-(2-hydroxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidin-4-yl}amino)phenoxy]-N-(2,6-difluorophenyl)piperidine-1-carboxamide hydrochloride

To a mixture of 2-[2-(4-{[3-chloro-4-(piperidin-4-yloxy)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethoxy]ethyl benzoate dihydrochloride (305 mg), 10% aqueous sodium carbonate solution (10 mL), ethyl acetate (15 mL) and tetrahydrofuran (5 mL) was added 2,6-difluorophenyl isocyanate (93 mg) with vigorous stirring. The mixture was stirred at room temperature for 2 hrs, water was added and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was dissolved in methanol (8 mL) and tetrahydrofuran (2 mL). 1N Aqueous sodium hydroxide solution (1 mL) was added, and the mixture was stirred at room temperature for 3 hrs. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to basic silica gel column chromatography (eluent, methanol:ethyl acetate=0:100→15:85). The object fraction was concentrated under reduced pressure. The residue was dissolved in ethyl acetate-ethanol, and 1N hydrochloric acid/ethyl acetate solution (0.5 mL) was added. The solvent was evaporated under reduced pressure and the obtained residue was crystallized from ethanol-ethyl acetate to give the title compound (202 mg) as a white powder.

1. extractionthe mixture was extracted with ethyl acetate
2. washThe ethyl acetate layer was washed with saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. dissolutionthe obtained residue was dissolved in methanol (8 mL)
6. addition1N Aqueous sodium hydroxide solution (1 mL) was added
7. stirringthe mixture was stirred at room temperature for 3 hrs
8. additionWater was added to the reaction mixture
9. extractionthe mixture was extracted with ethyl acetate
10. washThe ethyl acetate layer was washed with saturated brine
11. dry with materialdried over anhydrous magnesium sulfate
12. customThe solvent was evaporated under reduced pressure
13. concentrationThe object fraction was concentrated under reduced pressure
14. dissolutionThe residue was dissolved in ethyl acetate-ethanol
15. addition1N hydrochloric acid/ethyl acetate solution (0.5 mL) was added
16. customThe solvent was evaporated under reduced pressure
17. customthe obtained residue was crystallized from ethanol-ethyl acetate

ORDレコード

ord-9275b113359a49fb9629964f14972c92

出典データセット

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08178543B2