2-Amino-4,6-dimethyl pyrimidine → Methyl 3-[[(4,6-dimethylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-1-methyl-1H-indole-2-carboxylate

Beteiligte Stoffe

Reaktionsschritte

To a stirred suspension of 2.59 g (0.021 mole) of 2-amino-4,6-dimethylpyrimidine in 75 ml dry nitromethane at -10° was added 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 for 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 40 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. Methylene chloride was added and the layers separated. The aqueous solution was extracted with two additional portions of CH2Cl2 and the combined organic solutions were washed with H2O, dried over MgSO4 and evaporated in vacuo. Trituration of the residue with minimal CH2Cl2 afforded 2.02 g of the desired product as a white solid, m.p. 212°-215° (d). The infrared spectrum of the product included absorptions at 3215 and 3150 (NH), 1730 (C=O), 1710 (C=O), 1345 and 1150 (SO2) cm-1. 'H NMR (CDCl3 /DMSO-d6) δ2.43 (s, 6H, pyrimidine CH3), 3.88 (s, 6H, ester CH3 and N--CH3), 6.90 (s, 1H, pyrimidine CH), 7.23-7.75 (m, 3H, indole CH), 8.16-8.47 (m, 1H, indole CH), 10.30 (s, 1H, NH), 13.26 (br s, 1H, NH). Mass spectral analysis showed m/e 123, ##STR30##

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