Piperidine → 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-methyl-4-morpholino-pent-2-enenitrile

Temperature

105 °C

To a sealed tube was added 3-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidin-1-yl]-3-oxo-propanenitrile (900 mg, 1.91 mmol), ethanol (12 mL), piperidine (0.23 mL, 2.29 mmol) and 2-methyl-2-morpholino-propanal (0.49 mL, 2.86 mmol). The tube was sealed and heated to 105° C. for 24 hrs. The mixture was then cooled, concentrated and then dissolved in ethyl acetate (100 mL) and washed with 5% citric acid (100 ml) and then brine. The organic layer was dried (MgSO4), filtered and concentrated. The crude material was purified by Isolera (column size 100 g. Solvent system 4%-8% MeOH/EtOAc) to obtain 245 mg (21% yield) of the title compound. MS (pos. ion) m/z: 611 (M+1).

1. customThe tube was sealed
2. temperatureThe mixture was then cooled
3. concentrationconcentrated
4. dissolutiondissolved in ethyl acetate (100 mL)
5. washwashed with 5% citric acid (100 ml)
6. dry with materialThe organic layer was dried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude material was purified by Isolera (column size 100 g. Solvent system 4%-8% MeOH/EtOAc)

ORD record

ord-987a4b61ebe5401587d6d558d282e8b3

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09090621B2