Cyclopentylamine → 4-[2-chloro-4-({5-[2-(2-hydroxyethoxy)ethyl]-5H-pyrrolo[3,2-d]pyrimidin-4-yl}amino)phenoxy]-N-cyclopentylpiperidine-1-carboxamide hydrochloride

To a solution of 1,1′-carbonylbis(1H-imidazole) (162 mg) in tetrahydrofuran (5 mL) was added a solution of cyclopentylamine (85 mg) in tetrahydrofuran (1 mL), and the mixture was stirred at room temperature for 1 hr. A solution 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) and triethylamine (0.153 mL) in tetrahydrofuran (1 mL) was added, and the mixture was stirred overnight at room temperature. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The ethyl acetate layer 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 overnight at room temperature. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The ethyl acetate layer 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→10:90). 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 (188 mg) as a white powder.

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

ORD record

ord-c8d45ef7341e4a259527df19d4d59b92

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07507740B2