7-chloro-1,3-dihydroindol-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7-chloro-1,3-dihydro-2H-indol-2-one (8.0 g, 47.7 mmol) was slurried in H2SO4 (conc., 86 ml) and the mixture cooled to −45° C. A solution of fuming nitric acid (>90%, 3.34 g, 52.9 mmol) in H2SO4 (20 ml) was added drop wise, while maintaining the temperature at −45° C. throughout the addition. The mixture was allowed to slowly warm to RT and stirred overnight. The mixture was poured into stirred ice-cold water (1500 ml). A white precipitate resulted, and the slurry was aged at 0° C. for 1 hour. The solid was collected by filtration, triturated with cold water (2×), and dissolved into EtOAc (1 L). This mixture was filtered, washed with basic brine (containing sodium bicarbonate), dried over Na2SO4, filtered, and the volatiles removed in vacuum to give the titled compound. while maintaining the temperature at −45° C. throughout the addition to slowly warm to RT The mixture was poured A white precipitate resulted the slurry was aged at 0° C. for 1 hour The solid was collected by filtration triturated with cold water (2×) dissolved into EtOAc (1 L) This mixture was filtered washed with basic brine (containing sodium bicarbonate) dried over Na2SO4 filtered the volatiles removed in vacuum

Conditions: temp:-45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7-chloro-1,3-dihydro-2H-indol-2-one (8.0 g, 47.7 mmol) was slurried in H2SO4 (conc., 86 ml) and the mixture cooled to −45° C. A solution of fuming nitric acid (>90%, 3.34 g, 52.9 mmol) in H2SO4 (20 ml) was added drop wise, while maintaining the temperature at −45° C. throughout the addition. The mixture was allowed to slowly warm to RT and stirred overnight. The mixture was poured into stirred ice-cold water (1500 ml). A white precipitate resulted, and the slurry was aged at 0° C. for 1 hour. The solid was collected by filtration, triturated with cold water (2×), and dissolved into EtOAc (1 L). This mixture was filtered, washed with basic brine (containing sodium bicarbonate), dried over Na2SO4, filtered, and the volatiles removed in vacuum to give the titled compound. while maintaining the temperature at −45° C. throughout the addition to slowly warm to RT The mixture was poured A white precipitate resulted the slurry was aged at 0° C. for 1 hour The solid was collected by filtration triturated with cold water (2×) dissolved into EtOAc (1 L) This mixture was filtered washed with basic brine (containing sodium bicarbonate) dried over Na2SO4 filtered the volatiles removed in vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7-Chloro-1,3-dihydro-indol-2-one was condensed with 4-oxo-2,4,6,7-tetrahydro-pyrano[3,4-c]pyrrole-1-carbaldehyde to give the title compound.

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of sodium ethoxide prepared by heating 5.5 g. of sodium in 200 ml. of ethanol at 70° C. is added 17 g. of 7-chloro-3-hydrazono-oxindole over a period of 3.5 hours, and the resulting solution is heated at 70° C. for 24 hours. The solvent is evaporated in vacuo, the residue dissolved in water, acidified with 6 N. hydrochloric acid and the resulting precipitate recovered by filtering, washed three times with water, dried by suction and crystallized from methylene chloride/ether to obtain 7-chlorooxindole, 218°-220° C. by heating 5.5 g The solvent is evaporated in vacuo the residue dissolved in water hydrochloric acid and the resulting precipitate recovered by filtering washed three times with water dried by suction crystallized from methylene chloride/ether

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.3519 g 7-chlorooxindole (0.0021 mole) and 0.323 g azulene aldehyde (0.0021 mole) were dissolved in 30 mL dried ethanol. 1.5 mL pyrrolidine (1M) was then added and uniformly stirred at reflux temperature for two hours. After removal of dried ethanol, the results were extracted by dichloromethane and citric acid aqueous solution. The organic layer was collected, dried with anhydrous magnesium sulfate, filtered, concentrated under vacuum, and separated by silica gel column chromatography to give Z-form Compound 042 (0.3693 g). The total weight of 7-chlorooxindole-azulene was 0.3693 g (57.56%). at reflux temperature for two hours After removal of dried ethanol the results were extracted by dichloromethane and citric acid aqueous solution The organic layer was collected dried with anhydrous magnesium sulfate filtered concentrated under vacuum separated by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.3519 g 7-chlorooxindole (0.0021 mole) and 0.323 g azulene aldehyde (0.0021 mole) were dissolved in 30 mL dried ethanol. 1.5 mL pyrrolidine (1M) was then added and uniformly stirred at reflux temperature for two hours. After removal of dried ethanol, the results were extracted by dichloromethane and citric acid aqueous solution. The organic layer was collected, dried with anhydrous magnesium sulfate, filtered, concentrated under vacuum, and separated by silica gel column chromatography to give Z-form Compound 042 (0.3693 g). The total weight of 7-chlorooxindole-azulene was 0.3693 g (57.56%). at reflux temperature for two hours After removal of dried ethanol the results were extracted by dichloromethane and citric acid aqueous solution The organic layer was collected dried with anhydrous magnesium sulfate filtered concentrated under vacuum separated by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7-Chloro-1,3-dihydro-2H-indol-2-one (101.5 g) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (152 g) are reacted analogously to Example 1 Variant A. This gives the title compound as solid in an HPLC purity of 99% area (181.9 g, 97% of theory).