Chlorosulfonyl isocyanate → Methyl 3-[[(4-methoxy-6-methyl-pyrimidine-2-yl)aminocarbonyl]aminosulfonyl]-1-methyl-1H-indole-2-carboxylate

Beteiligte Stoffe

Reaktionsschritte

To a stirred suspension of 2.92 g (0.021 mole) of 2-amino-4-methoxy-6-methylpyrimidine in 75 ml dry CH3NO2 at -10° was addded dropwise under nitrogen via syringe 2.0 ml (0.023 mole) of chlorosulfonyl isocyanate at such a rate as to maintain the temperature below 0°. The resulting clear solution was stirred 0.5 hour at -5° to -10° and then contacted dropwise with a solution of 3.97 g (0.021 mole) of methyl 1-methyl-1H-indole-2-carboxylate dissolved in 25 ml of dry nitromethane. Upon completion of the addition, 2.95 g (0.022 mole) of aluminum (III) chloride was added in one portion. The reaction mixture was stirred at reflux for 3 hours, then cooled to room temperature and poured into 300 ml H2O. Dichloromethane was added and the layers were separated. The aqueous solution was extracted with two additional portions of CH2Cl2 and the combined organic solutions washed with H2O, dried over MgSO4 and evaporated in vacuo. Chromatography on silica gel with 5% acetone in CH2Cl2 afforded 1.63 g of the desired product as a white solid, m.p. 200°-203° (d). The infrared spectrum of the product included absorptions at 3190 (NH), 1715 (C=O), 1703 (C=O), 1340 and 1150 (SO2) cm-1, 'H NMR (CDCl3 /DMSO-d6) δ2.45 (s, 3H, pyrimidine CH3), 3.95 (s, 3H, OCH3), 4.0 (s, 6H, OCH3 and N--CH3), 6.37 (s, 1H, pyrimidine CH), 7.23-7.56 (m, 3H, indole CH), 8.18-8.47 (m, 1H, indole CH), 9.50 (s, 1H, NH), 13.08 (br s, 1H, NH). Mass spectral analysis showed m/e 139, ##STR31##

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