Sodium Hydroxide → N1-{4-[4-amino-1-(4-{[(2-morpholinoethyl)amino]methyl}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), N-(2-aminoethyl)morpholine (0.035 g, 0.27 mmol), and sodium triacetoxyborohydride (0.087 g, 0.41 mmol) in dichloroethane (1.4 mL) was shaken for 16 h at room temperature. Additiona portions of 1 N-(2-aminoethyl)morpholine (0.030 mL, 0.23 mmol) and sodium triacetoxyborohydride (0.087 g, 0.41 mmol) were added and the reaction mixture was shaken for 4 days. 1N NaOH (1 mL) was added and the precipitate was collected by filtration and purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 Å, 25 cm; 20-80% acetonitrile-0.05 M ammonium acetate over 25 min, 21 mL/min); the fraction eluting from 16.6-19.0 min was collected, concentrated, and lyopholized to afford N1-{4-[4-amino-1-(4-{[(2-morpholinoethyl)amino]methyl}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide as a white solid. (0.014 g, 0.021 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 9.88 (1H, s), 8.29-8.93 (2H, m), 8.11-8.17 (2H, m), 7.92-7.97 (1H, m), 7.83-7.86 (1H, m), 7.68-7.72 (1H, m), 7.46-7.51 (2H, m), 7.39 (1H, s), 7.34-7.38 (1H, m), 3.90 (3H, s), 3.50-3.52 (4H, m), 2.61-2.62 (2H, m), 2.40-2.50 (2H, obscured by DMSO peak), and 2.27-2.40 (6H, m); 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 10.96 min. MS: MH+ 665.2.

Provenance & Evidence