Diisopropylethylamine → Tert-butyl 4-((3-(2-(dimethylamino)pyrimidin-4-yl)-7-methoxynaphthalen-1-yl)amino)piperidine-1-carboxylate

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Reaction Steps

Synthesis of tert-butyl 4-(3-(2-(dimethylamino)pyrimidin-4-yl)-7-methoxynaphthalen-1-yl)amino)piperidine-1-carboxylate (142): To a slurry of 4-(4-amino-6-methoxynaphthalen-2-yl)-N,N-dimethylpyrimidin-2-amine (141) (203 mg) in 1,2-dichloroethane (12 ml) was added N,N-diisopropylethylamine (240 μl) and the mixture stirred at room temperature for 30 min until all of the material was in solution. Acetic acid (0.5 ml) was added followed by tert-butyl 4-oxopiperidine-1-carboxylate (165 mg) and sodium triacetoxyborohydride (219 mg). The mixture was stirred at room temperature for 24 hours. A further (100 mg) of both tert-butyl 4-oxopiperidine-1-carboxylate and triacetoxyborohydride was added and the mixture stirred for a further 8 hours. The mixture was poured into ethyl acetate (150 ml) washed with water (300 ml) and the organic layer dried over anhydrous magnesium sulfate. Evaporation to dryness gave a yellow oil that was purified by silica gel chromatography eluting with 20-30% ethyl acetate in hexanes to yield tert-butyl 4-((3-(2-(dimethylamino)pyrimidin-4-yl)-7-methoxynaphthalen-1-yl)amino)piperidine-1-carboxylate (142) as a yellow foam (215 mg). 1H NMR (CDCl3) 400 MHz δ 8.38 (d, J=5.2 Hz, 1H), 7.87 (s, 1H), 7.82 (d, J=9.2 Hz, 1H), 7.52 (m, 1H), 7.18 (dd, J=2.4 and 9.2 Hz 1H), 7.04 (m, 1H), 7.02 (d, J=5.6 Hz, 1H) 4.15-4.1 (m, 2H), 3.97 (s, 3H), 3.76 (m, 1H), 3.31 (s, 6H), 3.03 (m, 2H), 2.24 (m, 2H), 1.58-1.51 (m, 2H), 1.49 (s, 9H), LCMS m/e 478 (M+H)

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