反应详情

To a solution of 3-(acetylamino)-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide (Intermediate 32) (110 mg, 0.24 mmol) in 1,2-dichloroethane (10 mL) was added phosphorous oxychloride (0.175 mL, 1.9 mmol). The mixture was refluxed for 6 hours, cooled to room temperature and more phosphorous oxychloride (0.10 mL, 1.0 mmol) was added. The reaction was then refluxed for 4 hours. After cooling to room temperature the reaction was diluted with methanol, then poured onto a mixture of ice and concentrated HCl. This mixture was brought to a pH of 8 by addition of concentrated aqueous NaOH. The mixture was then extracted with ethyl acetate, concentrated under vacuum and purified by reverse-phase HPLC to give 7-(3-aminophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine (2 mg) as a yellow solid. 1H NMR (CD3OD): δ9.00 (s, 1H), 7.60 (d, J=7.87 Hz, 1H), 7.54 (s, 1H), 7.21 (t, J=7.78 Hz, 1H), 7.09 (s, 2H), 6.79 (dd, J=7.87 and 2.01 Hz, 1H), 3.77 (s, 6H), 3.73 (s, 3H), 2.56 (s, 3H). MS m/z 406 (M+1).

1. temperatureThe mixture was refluxed for 6 hours
2. temperatureThe reaction was then refluxed for 4 hours
3. temperatureAfter cooling to room temperature the reaction
4. extractionThe mixture was then extracted with ethyl acetate
5. concentrationconcentrated under vacuum
6. custompurified by reverse-phase HPLC