Morpholine → N1-(4-{4-amino-1-[4-(morpholinomethyl)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-2-fluoro-4-(trifluoromethyl)benzamide

Participants

Reaction Steps

A mixture of N1-{4-[4-amino-1-(4-formylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide (Intermediate 2) (0.075 g, 0.14 mmol), morpholine (0.024 mL, 0.27 mmol), and sodium triacetoxyborohydride (0.087 g, 0.409 mmol) in dichloroethane (1.4 mL) was shaken at ambient temperature for 16 h. Additional portions of morpholine (0.012 mL, 0.14 mmol), sodium triacetoxyborohydride (0.043 g, 0.20 mmol), and acetic acid (0.016 mL) were added and the reaction mixture was stirred at ambient temperature for 24 h. 1 N NaOH (1 mL) was added and the reaction mixture was filtered to afford a gray solid which was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 A, 25 cm; 10-60% acetonitrile—0.05 M ammonium acetate over 25 min, 21 mL/min); the fraction eluting from 21-23 min was collected, concentrated, and lyopholized to afford N1-(4-{4-amino-1-[4-(morpholinomethyl)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-2-fluoro-4-(trifluoromethyl)benzamide as a white solid (0.007 g, 0.011 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 9.93 (1H, s), 8.34-8.37 (2H, m), 8.14-8.18 (2H, m), 7.97-8.02 (1H, m), 7.87-7.91 (1H, m), 7.73-7.76 (1H, m), 7.45-7.51 (2H, m), 7.44 (1H, s), 7.38-7.43 (1H, m), 3.41-3.59 (8H, m), and 3.36 (2H, s); RP-HPLC (Hypersil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile—0.1 M ammonium acetate over 15 min, 1 mL/min). Rt 11.72 min. MS: MH+ 622.2.

Provenance & Evidence