S(O)(O)(=O)=O.[NH:6]1[CH:10]=[CH:9][N:8]=[C:7]1[NH2:11].[F:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]([C:25](OCC)=[O:26])[C:20](OCC)=[O:21])=[CH:15][CH:14]=1.N12CCCN=C1CCCCC2.Cl>CN(C=O)C.O>[F:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]2[C:25]([OH:26])=[N:11][C:7]3[N:6]([CH:10]=[CH:9][N:8]=3)[C:20]=2[OH:21])=[CH:17][CH:18]=17.2 g (39.3 mmol) 1H-Imidazol-2-ylamine sulfate are dissolved in 45 mL DMF. 10 g (39.3 mmol) diethyl (4-fluorophenyl)malonate is added. After dropwise addition of 17.6 mL (118 mmol) 1,8-diazabicyclo[5.4.0]undec-7-ene the reaction mixture is stirred at 100° C. over night. The DMF has been removed and the darkbrown oily residue treated with 150 mL water (complete dissolution). 2M HCl (60 mL) is added at room temperature until a pH of 1. After stirring for 1 h at ice bath cooling the formed crystals are collected by filtration to yield the product (5.78 g=53.9%), which is used without further purification. Another crop of 0.48 g (4.5%) is obtained by treating the solid residue in the flask with water and 2M HCl. After stirring for one hour the crystals are collected.
Loading…
