N-methyl-2-pyrrolidone → 2-(2-(4-((3-chloro-4-(3-(trifluoromethyl)phenoxy)phenyl)amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethoxy)ethan-1-ol

Temperature

120 °C

A mixture of 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethoxy]ethyl benzoate (1.037 g), 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (863 mg) and 1-methyl-2-pyrrolidone (10 mL) was stirred at 120° C. for 1.5 hrs. Water and saturated aqueous sodium hydrogen carbonate solution were added to the reaction mixture and the mixture was extracted with ethyl acetate. The ethyl acetate layer washed successively with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate:hexane=50:50→100:0). The object fraction was concentrated under reduced pressure. To a solution of the residue (1.420 g) in methanol (30 mL) was added 1N aqueous sodium hydroxide solution (3 mL), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, 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 silica gel column chromatography (eluent, methanol:ethyl acetate=0:100→5:95). The object fraction was concentrated under reduced pressure. The precipitated crystals were collected by filtration, and washed with diethyl ether. The crude crystals were recrystallized from ethyl acetate-diisopropyl ether to give the title compound (933 mg) as a white powder.

1. extractionthe mixture was extracted with ethyl acetate
2. washThe ethyl acetate layer washed successively with water and saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. concentrationThe object fraction was concentrated under reduced pressure
6. additionTo a solution of the residue (1.420 g) in methanol (30 mL) was added 1N aqueous sodium hydroxide solution (3 mL)
7. stirringthe mixture was stirred at room temperature for 1 hr
8. concentrationThe reaction mixture was concentrated under reduced pressure, water
9. additionwas 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. filtrationThe precipitated crystals were collected by filtration
16. washwashed with diethyl ether
17. customThe crude crystals were recrystallized from ethyl acetate-diisopropyl ether

ORD record

ord-c4bcf95170ce4ab1a0e5e7f5db86573a

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07507740B2