Uses
6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)indolin-2-one is useful for preparation of imidazopyridazines as therapeutic kinase inhibitors.
Synthesis
The general procedure for the synthesis of 2-oxoindoline-6-boronic acid pinacol ester from 6-bromo-2-indolone and bis(pinacolato)diboron (898 mg, 3.54 mmol), potassium acetate (694 mg, 7.07 mmol) and Pd(dppf)Cl2-CH2Cl2 (96.0 mg, 0.118 mmol). The above mixture was dissolved in 1,2-dimethoxyethane (DME, 17 mL). The reaction system was heated and reacted at 80 °C overnight. Upon completion of the reaction, the contents of the four reaction vials were combined, the reaction solution was concentrated and purified by column chromatography (cyclohexane/ethyl acetate as eluent) to afford the target compound, 2-oxoindoline-6-boronic acid pinacol ester, as a white solid (2.27 g, 75% yield, 80% purity). The structure of the product was confirmed by 1H NMR (500 MHz, CDCl3): δ 8.57 (broad single peak, 1H), 7.48 (double peak, J=7.3 Hz, 1H), 7.31 (single peak, 1H), 7.23 (double peak, J=7.3 Hz, 1H), 3.55 (single peak, 2H), 1.33 (single peak, 12H).LC-MS (ESI, m/z) analysis showed that: retention time was 0.5 mm. z) analysis showed retention time Rt = 2.75 min and molecular ion peak m/z = 260 ([M+H]+, HPLC method E).
References
[1] Patent: WO2015/144290, 2015, A1. Location in patent: Page/Page column 85
[2] Patent: WO2015/39172, 2015, A1. Location in patent: Page/Page column 60
[3] Patent: WO2011/15641, 2011, A1. Location in patent: Page/Page column 128
[4] Patent: WO2011/101640, 2011, A1. Location in patent: Page/Page column 106
[5] Patent: WO2008/23161, 2008, A1. Location in patent: Page/Page column 120
