2-(4-oxopentyl)isoindole-1,3-dione

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5.33 gm (21.7 mMol) 4-(4-fluorobenzoyl)aminophenylhydrazine and 5.03 gm (21.8 mMol) 5-phthalimidyl-2-pentanone in 100 mL ethanol were added 2 mL concentrated hydrochloric acid and the reaction mixture was heated at 80° C. for 14 hours. To the reaction mixture were then added an additional 3 mL concentrated hydrochloric acid and heating continued for an additional 6 hours. The reaction mixture was then cooled to 0° C. and 100 mL hexane were slowly added. The solid which formed was filtered and washed with hexane and provided, after drying, 6.67 gm of the desired compound. The mother liquor was concentrated under reduced pressure and then subjected to silica gel chromatography, eluting with 1:1 hexane:ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide an additional 0.63 gm of product. Overall yield was 7.3 gm (76%). heating The reaction mixture was then cooled to 0° C. The solid which formed was filtered washed with hexane provided after drying The mother liquor was concentrated under reduced pressure eluting with 1:1 hexane Fractions containing product concentrated under reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 24.59 g (132.8 mmol) of potassium phthalimide are added to a solution of 14.3 ml (124.4 mmol) of 5-chloro-2-pentanone in 100 ml of DMF and the mixture is left to stir at room temperature for 3 h and at 60° C. for 30 h. After filtering, the filtrate is partitioned between water and dichloromethane. The phases are separated and the organic phase is washed successively with water, twice with an 0.2N solution of NaOH and water and then dried over sodium sulfate. After filtering, the solvent is removed in vacuo and the residue is chromatographed through silica gel using heptane/ethyl acetate=6/4. 9.8 g (34%) of (14.1) are obtained after concentrating the product fractions. the mixture is left After filtering the filtrate is partitioned between water and dichloromethane The phases are separated the organic phase is washed successively with water, twice with an 0.2N solution of NaOH and water dried over sodium sulfate After filtering the solvent is removed in vacuo the residue is chromatographed through silica gel

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

Procedure: Using General Procedure B: Reaction of 2-(4-oxo-pentyl)-isoindole-1,3-dione (Abdel-Monem, M M et al. J. Med. Chem. 1974, 17, 447-451) in CH2Cl2 and 1-pyridin-2-yl-ethylamine with NaBH(OAc)3 gave 2-[4-(1-pyridin-2-yl-ethylamino)-pentyl]-isoindole-1,3-dione as a colorless oil.

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

Procedure: Using General Procedure B: Reaction of 2-(4-oxo-pentyl)-isoindole-1,3-dione (Abdel-Monem, M M et al. J. Med. Chem. 1974, 17, 447-451) in CH2Cl2 and 1-pyridin-2-yl-ethylamine with NaBH(OAc)3 gave 2-[4-(1-pyridin-2-yl-ethylamino)-pentyl]-isoindole-1,3-dione as a colorless oil.

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 12.4 g of 8-amino-5-(3,4-dichlorophenoxy)-6-methoxy-4-methylquinoline (36 mM) and 11.6 g of 4-oxo-1-phthalimidopentane (50 mM), in glacial acetic acid was stirred for 15 min under nitrogen and 2.6 g of sodium borohydride (70 mM) was added portionwise maintaining the temperature 25-35° C. After the addition, the reaction mixture was stirred for 30 min and then poured into ice cold solution of concentrated sodium hydroxide. The resulting precipitate was filtered and chromatographed over silica gel. Elution with hexanes:ethyl acetate 90:10 yielded the expected product of 5-(3,4-dichlorophenoxy)-6-methoxy-4-methyl-8-[(4-phthalimido-1-methylbutyl)amino]quino line which was crystallized from ether to give 12.4 g (22 mM) of yellow crystalline product. After the addition The resulting precipitate was filtered chromatographed over silica gel Elution with hexanes:ethyl acetate 90:10

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5.33 gm (21.7 mMol) 4-(4-fluorobenzoyl)aminophenylhydrazine and 5.03 gm (21.8 mMol) 5-phthalimidyl-2-pentanone in 100 mL ethanol were added 2 mL concentrated hydrochloric acid and the reaction mixture was heated at 80° C. for 14 hours. To the reaction mixture were then added an additional 3 mL concentrated hydrochloric acid and heating continued for an additional 6 hours. The reaction mixture was then cooled to 0° C. and 100 mL hexane were slowly added. The solid which formed was filtered and washed with hexane and provided, after drying, 6.67 gm of the desired compound. The mother liquor was concentrated under reduced pressure and then subjected to silica gel chromatography, eluting with 1:1 hexane:ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide an additional 0.63 gm of product. Overall yield was 7.3 gm (76%). heating The reaction mixture was then cooled to 0° C. The solid which formed was filtered washed with hexane provided after drying The mother liquor was concentrated under reduced pressure eluting with 1:1 hexane Fractions containing product concentrated under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5.33 gm (21.7 mMol) 4-(4-fluorobenzoyl)aminophenylhydrazine and 5.03 gm (21.8 mMol) 5-phthalimidyl-2-pentanone in 100 mL ethanol were added 2 mL concentrated hydrochloric acid and the reaction mixture was heated at 80° C. for 14 hours. To the reaction mixture were then added an additional 3 mL concentrated hydrochloric acid and heating continued for an additional 6 hours. The reaction mixture was then cooled to 0° C. and 100 mL hexane were slowly added. The solid which formed was filtered and washed with hexane and provided, after drying, 6.67 gm of the desired compound. The mother liquor was concentrated under reduced pressure and then subjected to silica gel chromatography, eluting with 1:1 hexane:ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide an additional 0.63 gm of product. Overall yield was 7.3 gm (76%). heating The reaction mixture was then cooled to 0° C. The solid which formed was filtered washed with hexane provided after drying The mother liquor was concentrated under reduced pressure eluting with 1:1 hexane Fractions containing product concentrated under reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 24.59 g (132.8 mmol) of potassium phthalimide are added to a solution of 14.3 ml (124.4 mmol) of 5-chloro-2-pentanone in 100 ml of DMF and the mixture is left to stir at room temperature for 3 h and at 60° C. for 30 h. After filtering, the filtrate is partitioned between water and dichloromethane. The phases are separated and the organic phase is washed successively with water, twice with an 0.2N solution of NaOH and water and then dried over sodium sulfate. After filtering, the solvent is removed in vacuo and the residue is chromatographed through silica gel using heptane/ethyl acetate=6/4. 9.8 g (34%) of (14.1) are obtained after concentrating the product fractions. the mixture is left After filtering the filtrate is partitioned between water and dichloromethane The phases are separated the organic phase is washed successively with water, twice with an 0.2N solution of NaOH and water dried over sodium sulfate After filtering the solvent is removed in vacuo the residue is chromatographed through silica gel

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 24.59 g (132.8 mmol) of potassium phthalimide are added to a solution of 14.3 ml (124.4 mmol) of 5-chloro-2-pentanone in 100 ml of DMF and the mixture is left to stir at room temperature for 3 h and at 60° C. for 30 h. After filtering, the filtrate is partitioned between water and dichloromethane. The phases are separated and the organic phase is washed successively with water, twice with an 0.2N solution of NaOH and water and then dried over sodium sulfate. After filtering, the solvent is removed in vacuo and the residue is chromatographed through silica gel using heptane/ethyl acetate=6/4. 9.8 g (34%) of (14.1) are obtained after concentrating the product fractions. the mixture is left After filtering the filtrate is partitioned between water and dichloromethane The phases are separated the organic phase is washed successively with water, twice with an 0.2N solution of NaOH and water dried over sodium sulfate After filtering the solvent is removed in vacuo the residue is chromatographed through silica gel

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

Procedure: Using General Procedure B: Reaction of 2-(4-oxo-pentyl)-isoindole-1,3-dione (Abdel-Monem, M M et al. J. Med. Chem. 1974, 17, 447-451) in CH2Cl2 and 1-pyridin-2-yl-ethylamine with NaBH(OAc)3 gave 2-[4-(1-pyridin-2-yl-ethylamino)-pentyl]-isoindole-1,3-dione as a colorless oil.

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

Procedure: Using General Procedure B: Reaction of 2-(4-oxo-pentyl)-isoindole-1,3-dione (Abdel-Monem, MM et al. J. Med. Chem. 1974, 17, 447-451) in CH2Cl2 and 1-pyridin-2-yl-ethylamine with NaBH(OAc)3 gave 2-[4-(1-pyridin-2-yl-ethylamino)-pentyl]-isoindole-1,3-dione as a colorless oil.

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5.33 gm (21.7 mMol) 4-(4-fluorobenzoyl)aminophenylhydrazine and 5.03 gm (21.8 mMol) 5-phthalimidyl-2-pentanone in 100 mL ethanol were added 2 mL concentrated hydrochloric acid and the reaction mixture was heated at 80° C. for 14 hours. To the reaction mixture were then added an additional 3 mL concentrated hydrochloric acid and heating continued for an additional 6 hours. The reaction mixture was then cooled to 0° C. and 100 mL hexane were slowly added. The solid which formed was filtered and washed with hexane and provided, after drying, 6.67 gm of the desired compound. The mother liquor was concentrated under reduced pressure and then subjected to silica gel chromatography, eluting with 1:1 hexane:ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide an additional 0.63 gm of product. Overall yield was 7.3 gm (76%). heating The reaction mixture was then cooled to 0° C. The solid which formed was filtered washed with hexane provided after drying The mother liquor was concentrated under reduced pressure eluting with 1:1 hexane Fractions containing product concentrated under reduced pressure