2-(二甲氨基)异吲哚-1,3-二酮

反应条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of phenylmagnesium bromide in THF (11.6 mmol) was slowly added to a solution of phthalimide 16 (10.5 mmol) in THF (110 ml) at −78 ° C. and stirred under argon for 15 minutes. The mixture was then progressively warmed to −30 ° C. for 1 hour. The reaction was quenched with a saturated aqueous solution of NH4Cl (15 ml) and the aqueous layer extracted with Et2O. The combined organic layers were washed with brine (20 ml), dried over MgSO4 and the solvent was evaporated under reduced pressure. The resulting crude product was purified by silica gel chromatography with (1:2) EtOAc:hexane, to give 80% yield of the desired product. The reaction was quenched with a saturated aqueous solution of NH4Cl (15 ml) the aqueous layer extracted with Et2O The combined organic layers were washed with brine (20 ml) dried over MgSO4 the solvent was evaporated under reduced pressure The resulting crude product was purified by silica gel chromatography with (1:2) EtOAc

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the suspension of phthalic anhydride (62.5 mmol) in toluene (500 ml), N,N-dimethyl hydrazine dihydrochloride (50 mmol) and diethyl-phenyl-amine (90 mmol) were added. The reaction mixture was refluxed for 18 hours while removing the formed water via a Dean-Stark trap. Then, toluene was evaporated under reduced pressure and the resulting crude was purified on silica gel chromatography with (1:5) EtOAc:dichloromethane, to give the desired product in 85% yield. were added The reaction mixture was refluxed for 18 hours while removing the formed water via a Dean-Stark trap Then, toluene was evaporated under reduced pressure the resulting crude was purified on silica gel chromatography with (1:5) EtOAc

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Phthalazine derivatives of formula IA were prepared as described in FIG. 8 and as further detailed in Example 4. The commercially available phthalic anhydride was reacted with N,N-dimethyl hydrazine to give 2-(dimethylamino)isoindoline-1,3-dione 16 in good yield [Hanefeld W et al. J Heterocyclic Chem. 1996;33:1443]. Then, 16 was reacted with phenylmagnesium bromide, to lead to the intermediate 17 in good yield [Deniau E et al. Tetrahedron: Asym. 2003;14:2253], which in turn was quantitatively converted by reaction with hydrazine to 4-phenylphthalazin-1(2H)-one 18 [Saito Y et al. Synthesis 2001;2:221]. Finally, the N-amidation product 19 (Compound I) was the major product obtained in good yield whatever the experimental conditions. Two different carbamoyl chlorides were used (R1=CH3—compound 19a; and i-Pr—compound 19b) for the preparation of phthalazine derivatives. (FIG. 8). were prepared

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of phenylmagnesium bromide in THF (11.6 mmol) was slowly added to a solution of phthalimide 16 (10.5 mmol) in THF (110 ml) at −78 ° C. and stirred under argon for 15 minutes. The mixture was then progressively warmed to −30 ° C. for 1 hour. The reaction was quenched with a saturated aqueous solution of NH4Cl (15 ml) and the aqueous layer extracted with Et2O. The combined organic layers were washed with brine (20 ml), dried over MgSO4 and the solvent was evaporated under reduced pressure. The resulting crude product was purified by silica gel chromatography with (1:2) EtOAc:hexane, to give 80% yield of the desired product. The reaction was quenched with a saturated aqueous solution of NH4Cl (15 ml) the aqueous layer extracted with Et2O The combined organic layers were washed with brine (20 ml) dried over MgSO4 the solvent was evaporated under reduced pressure The resulting crude product was purified by silica gel chromatography with (1:2) EtOAc

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the suspension of phthalic anhydride (62.5 mmol) in toluene (500 ml), N,N-dimethyl hydrazine dihydrochloride (50 mmol) and diethyl-phenyl-amine (90 mmol) were added. The reaction mixture was refluxed for 18 hours while removing the formed water via a Dean-Stark trap. Then, toluene was evaporated under reduced pressure and the resulting crude was purified on silica gel chromatography with (1:5) EtOAc:dichloromethane, to give the desired product in 85% yield. were added The reaction mixture was refluxed for 18 hours while removing the formed water via a Dean-Stark trap Then, toluene was evaporated under reduced pressure the resulting crude was purified on silica gel chromatography with (1:5) EtOAc

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Phthalazine derivatives of formula IA were prepared as described in FIG. 8 and as further detailed in Example 4. The commercially available phthalic anhydride was reacted with N,N-dimethyl hydrazine to give 2-(dimethylamino)isoindoline-1,3-dione 16 in good yield [Hanefeld W et al. J Heterocyclic Chem. 1996;33:1443]. Then, 16 was reacted with phenylmagnesium bromide, to lead to the intermediate 17 in good yield [Deniau E et al. Tetrahedron: Asym. 2003;14:2253], which in turn was quantitatively converted by reaction with hydrazine to 4-phenylphthalazin-1(2H)-one 18 [Saito Y et al. Synthesis 2001;2:221]. Finally, the N-amidation product 19 (Compound I) was the major product obtained in good yield whatever the experimental conditions. Two different carbamoyl chlorides were used (R1=CH3—compound 19a; and i-Pr—compound 19b) for the preparation of phthalazine derivatives. (FIG. 8). were prepared

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of phenylmagnesium bromide in THF (11.6 mmol) was slowly added to a solution of phthalimide 16 (10.5 mmol) in THF (110 ml) at −78 ° C. and stirred under argon for 15 minutes. The mixture was then progressively warmed to −30 ° C. for 1 hour. The reaction was quenched with a saturated aqueous solution of NH4Cl (15 ml) and the aqueous layer extracted with Et2O. The combined organic layers were washed with brine (20 ml), dried over MgSO4 and the solvent was evaporated under reduced pressure. The resulting crude product was purified by silica gel chromatography with (1:2) EtOAc:hexane, to give 80% yield of the desired product. The reaction was quenched with a saturated aqueous solution of NH4Cl (15 ml) the aqueous layer extracted with Et2O The combined organic layers were washed with brine (20 ml) dried over MgSO4 the solvent was evaporated under reduced pressure The resulting crude product was purified by silica gel chromatography with (1:2) EtOAc

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the suspension of phthalic anhydride (62.5 mmol) in toluene (500 ml), N,N-dimethyl hydrazine dihydrochloride (50 mmol) and diethyl-phenyl-amine (90 mmol) were added. The reaction mixture was refluxed for 18 hours while removing the formed water via a Dean-Stark trap. Then, toluene was evaporated under reduced pressure and the resulting crude was purified on silica gel chromatography with (1:5) EtOAc:dichloromethane, to give the desired product in 85% yield. were added The reaction mixture was refluxed for 18 hours while removing the formed water via a Dean-Stark trap Then, toluene was evaporated under reduced pressure the resulting crude was purified on silica gel chromatography with (1:5) EtOAc

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Phthalazine derivatives of formula IA were prepared as described in FIG. 8 and as further detailed in Example 4. The commercially available phthalic anhydride was reacted with N,N-dimethyl hydrazine to give 2-(dimethylamino)isoindoline-1,3-dione 16 in good yield [Hanefeld W et al. J Heterocyclic Chem. 1996;33:1443]. Then, 16 was reacted with phenylmagnesium bromide, to lead to the intermediate 17 in good yield [Deniau E et al. Tetrahedron: Asym. 2003;14:2253], which in turn was quantitatively converted by reaction with hydrazine to 4-phenylphthalazin-1(2H)-one 18 [Saito Y et al. Synthesis 2001;2:221]. Finally, the N-amidation product 19 (Compound I) was the major product obtained in good yield whatever the experimental conditions. Two different carbamoyl chlorides were used (R1=CH3—compound 19a; and i-Pr—compound 19b) for the preparation of phthalazine derivatives. (FIG. 8). were prepared