2-Methoxy-5-(4,4,5,5-tetramethyl-[1,3,2] dioxaborolan-2-yl)-pyridin-3-ylamine

Uses

It is used as a pharmaceutical intermediate.

Synthesis

Step A: Synthesis of 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine [00403] Degassed 5-bromo-2-methoxypyridin-3-amine (2 g, 9.85 mmol), 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl pinacol ester (3.00 g, 11.82 mmol), Pd(dppf)2Cl2-CH2Cl2 adduct (0.804 g, 0.985 mmol) and potassium acetate (3.87 g, 39.4 mmol) in 1,4-dioxane (50 mL) was heated at 100 °C for 18 h followed by stirring at room temperature overnight. Upon completion of the reaction, the mixture was filtered through a Celite pad and washed with EtOAc. The filtrate was concentrated and the residual solvent was removed by azeotropy with CH2Cl2/hexane. The crude product was dissolved in CH2Cl2 and purified by silica gel column chromatography (elution gradient: 0-100% EtOAc/hexane) to afford 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine (3.9 g, 9.36 mmol, 95% yield) as a light brown solid.1H NMR (400 MHz, DMSO-d6) was performed on a 1H NMR pad. MHz, DMSO-d6) δ ppm: 1.26 (s, 12H), 3.87 (s, 3H), 4.92 (s, 2H), 7.12 (d, J = 1.46 Hz, 1H), 7.63 (d, J = 1.37 Hz, 1H); ES LC-MS m/z = 251.4 (M + H)+.

References

[1] Patent: WO2012/174312, 2012, A2. Location in patent: Page/Page column 287
[2] Patent: WO2014/6554, 2014, A1. Location in patent: Page/Page column 43
[3] Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 2091 - 2106
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 18, p. 7381 - 7399
[5] Patent: WO2014/60431, 2014, A1. Location in patent: Page/Page column 85