3-Methoxypropylamine → HCID 22346801, compound

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), 3-methoxypropylamine (0.024 g, 0.27 mmol), and sodium triacetoxyborohydride (0.087 g, 0.41 mmol) in dichloroethane (1.4 mL) was shaken at room temperature for 3 days. Additional portions of 3-methoxypropylamine (0.1 mL, 1 mmol) and sodium triacetoxyborohydride (0.085 g, 0.40 mmol) were added and the mixture was shaken for 3 days. Acetic acid (0.1 mL) was added and the reaction mixture was shaken for 4 days. An additional portion of sodium triacetoxyborohydride (0.100 g, 0.470 mmol) was added and the reaction mixture was shaken for 16 h. 1N NaOH (1 mL) was added and the reaction mixture was concentrated, dissolved in DMF (2 mL), filtered through a syring-tip Acrodisc filter, 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 18.0-19.7 min was collected, concentrated, and lyopholized to afford N1-{4-[4-amino-1-(4-{[(3-methoxypropyl)amino]methyl}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide as a white solid (0.009 g, 0.014 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 9.93 (1H, s), 8.33-8.38 (2H, m), 8.18-8.20 (2H, m), 7.97-8.01 (1H, m), 7.87-7.91 (1H, m), 7.73-7.76 (1H, m), 7.54-7.64 (5H, m), 7.31-7.45 (2H, m), 3.95 (3H, s), 3.85-3.89 (2H, m), 3.38 (2H, s), 2.55-2.68 (2H, m), and 1.70-1.74 (2H, 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 10.58 min. MS: MH+ 624.2.

Provenance & Evidence