Preparation background and overview of 2-(dimethylamino)pyridine-5-boronic acid pinacol ester
2-(Dimethylamino)pyridine-5-boronic acid pinacol ester is an organic intermediate potassium bicarbonate that can be used in the Suzuki reaction. 2-(Dimethylaminoisopropylpyridine)pyridine-5-boronic acid pinacol ester can be used as the reaction raw material to prepare the intermediate 5-bromo-N, N-dimethylpyridine-2- The amine is then further reacted with pinacol diboronate to prepare it.
Preparation of 2-(dimethylamino)pyridine-5-boronic acid pinacol ester
Preparation of 2-(dimethylamino)pyridin-5-boronic acid pinacol ester Step 1: 5-bromo-N, N-dimethylpyridin-2-amine
To a solution of 5-bromopyridin-2-amine (1.0g, 5.8mmol) in THF (25mL), add NaH (0.90g, 23.1mmol), stir at 0°C for 10 minutes, then add CH3I (1mL, 16 mmol) and stir for 1 h, add water (30 mL), and extract with ethyl acetate (3 × 30 mL). The combined organic layers were washed with brine, dried over Na2SO4, concentrated and purified by column chromatography on silica gel (ethyl acetate in petroleum ether, 10% v/v) to give the title compound, yield 1.1 g, 94%, white solid. LCMS: 203[M+2]+. 1HNMR (MHz, DMSO-d6) δ2.99 (s, 6H), 6.61 (d, J=9.6Hz, 1H), 7.62 (dd, J=9.2, 2.8Hz, 1H) , 8.12 (d, J=2.4Hz, 1H).
Preparation of 2-(dimethylamino)pyridine-5-boronic acid pinacol ester Step 2: 2-(dimethylamino)pyridine-5-boronic acid pinacol ester
To a solution of 5-bromo-N,N-dimethylpyridin-2-amine (2.5g, 11.6mmol) and pinacol diborate (4.4g, 17.5mmol) in dioxane (100mL) Potassium acetate (3.4g, 35mmol) and PdCl2 (dppf)2 (0.95g, 1.1mmol) were added. The mixture was degassed with nitrogen and heated at 85°C overnight. The reaction mixture was concentrated under reduced pressure to provide crude product, which was purified by column chromatography (ethyl acetate in petroleum ether, 15% v/v) to give compound 2-(dimethylamino)pyridine-5- Pinacolate borate. 1HNMR (MHz, DMSO-d6) δ1.27 (s, 12H), 3.05 (s, 6H), 6.58 (d, J=8.8Hz, 1H), 7.67 (dd, J= 8.4, 1.6Hz, 1H), 8.32 (d, J=1.2Hz, 1H).
References
[1] WO2011130628 Treatment of cancers having k-ras mutations using PI3 kinase and HDAC inhibitors and preparation of bifunctional thienopyrimidine compounds that inhibit both enzymes
