4-[4-amino-3-(3-methoxy-4-[(1-methyl-1H-2-indolyl)-carbonyl]aminophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyridiniumolate → N2-{4-[4-amino-1-(4-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide

Participants

Reaction Steps

A suspension of 4-[4-amino-3-(3-methoxy-4-{[(1-methyl-1H-2-indolyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyridiniumolate (0.200 g, 0.00039 mol) and 10% palladium on carbon (0.042 g, 0.00004 mol) in acetic acid (3 mL) was reacted with sodium hypophosphite monohydrate (0.063 g, 0.00059 mol) at 60° C. for 2 hours. Additional 10% palladium on carbon (0.042 g, 0.00004 mol) and sodium hypophosphite (0.045 g, 0.00042 mol) was added and the mixture was stirred for 24 hours. The solvent was removed in vacuo and the residue was slurried in methanol for 4 hours. The mixture was filtered through Celite® 521, washing with methanol. The solvent was removed in vacuo and the residue was purified by preparative RP-HPLC (Rainin C18, 8 mm, 300 A, 25 cm; 50% isocratic for five minutes, then 50%-100% acetonitrile—0.1M ammonium acetate over 25 min, 21 mL/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyopholyzed to give N2-{4-[4-amino-1-(4-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide (0.020 g, 0.00004 mol) as a white solid: 1H NMR (DMSO-d6, 400 MHz) δ 9.48 (s, 1H) 8.72 (d, 2H), 8.47 (s, 1H), 8.42 (d, 2H), 8.20 (d, 1H), 7.72 (d, 1H), 7.60 (d, 1H), 7.48 (s, 1H), 7.42 (d, 1H), 7.36 (s, 1H) 7.34 (t, 1H), 7.16 (t, 1H), 4.05 (s, 3H), 3.99 (s, 1H); RP-HPLC (Delta Pak C18, 5 μm, 300A, 15 cm; 5%-85% acetonitrile—0.1M ammonium acetate over 20 min, 1 mL/min) Rt 19.50 min.;

Provenance & Evidence