Phthalimide, N-(2-formylethyl)- → 2-(3-((7-Methoxy-3-(2-(methylamino)pyrimidin-4-yl)naphthalen-1-yl)amino)propyl)isoindoline-1,3-dione

Participants

Reaction Steps

To a slurry of 4-(4-amino-6-methoxynaphthalen-2-yl)-N-methylpyrimidin-2-amine (150 mg, 0.42 mmol) in 1,2-dichloromethane (10 ml) was added N,N-diisopropylethylamine (250 μl) followed by acetic acid (0.5 ml), 3-(1,3-dioxoisoindolin-2-yl)propanal (140 mg) and sodium triacetoxyborohydride (200 mg). The mixture was stirred at room temperature for 24 hours before being poured into ethyl acetate (100 ml) washed with water (250 ml) and dried over anhydrous magnesium sulfate. Evaporation to dryness gave a yellow oil which was purified by silica gel chromatography eluting with 40-60% ethyl acetate in hexanes to yield 2-(3-((7-methoxy-3-(2-(methylamino)pyrimidin-4-yl)naphthalen-1-yl)amino)propyl)isoindoline-1,3-dione 181 as a yellow foam (95 mg). 1H NMR (CDCl3) 400 MHz δ 8.34 (d, J=5.2 Hz, 1H), 7.87 (s, 1H), 7.86-7.83 (m, 3H), 7.8 (d, J=8.8 Hz, 1H), 7.75-7.71 (m, 2H), 7.34 (s, 1H), 7.31 (d, J=2.4 Hz, 1H), 7.18 (dd, J=2.4 and 8.8 Hz, 1H), 7.08 (d, J=4.8 Hz, 1H), 5.24 (m, 1H), 4.9 (m, 1H), 4.04 (s, 3H), 3.9 (t, J=6.0 Hz 2H), 3.5 (t, J=6.0 Hz, 2H), 3.11 (d, J=5.2 Hz, 3H), 2.24 (m, 2H), 2.2-2.14 (m, 2H), LCMS m/e 468 (M+H)

Provenance & Evidence