[Cl:1][C:2]1[CH:11]=[C:10]([Cl:12])[CH:9]=[C:8]2[C:3]=1[C:4](=O)[CH:5]=[C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[NH:7]2.ClS([N:23]=C=O)(=O)=O.Cl>C(#N)C.CO>[NH2:23][C:4]1[C:3]2[C:8](=[CH:9][C:10]([Cl:12])=[CH:11][C:2]=2[Cl:1])[N:7]=[C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:5]=1A 12-L three-neck flask equipped with a mechanical mixer, a condenser, and thermocouple was charged with Compound 4 (0.94 mole, 269.1 g) in acetonitrile (ACN; about 4 L), after which chlorosulfonyl isocyanate (0.99 mole, 86 mL) was added (dropwise) via the dropping funnel. Upon completion of the addition, the resulting reaction mixture was refluxed for about 28 minutes. The pH of the mixture was about 0 at this point. The mixture then was cooled slightly, while adding saturated HCl in methanol (MeOH; 500 mL). Subsequently, the mixture was refluxed for about 1 hour, and then allowed to cool to room temperature overnight, during which time crystals formed. The crystals were collected on a sintered glass frit and rinsed with acetonitrile (400 mL and 500 mL). The filter cake was then transferred to a 12 L reactor with a mechanical stirrer. Deionized (DI) water (900 mL) and saturated Na2CO3 (500 mL) were added to afford mixture having a pH of about 10. Next, the solids in the mixture were collected and slurry rinsed with DI water (3×500 mL). The rinsed product was dried via lyophilization to afford about 268.79 g (63.3% yield) of Compound 5.
Wird geladen…
