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

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:0.00; pressure:0.00; stir:

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

Procedure: A stirred mixture of 8-amino-6-methoxy-4-methyl-5-[5-(2-thienyl) pentoxy] quinoline (4.00 g, 0.0108 mol) and 4-bromo-1-phthalimidopentane (BPP) (6.40 g, 0.0216 mol) was heated at 110°-115° C. while Et3N (4 ml) was slowly added during 25 min. After 4 h at 115°-120° C., more BPP (6.4 g, 0.0216 mol) and Et3N (2 ml during 10 min) were added and heating was continued for 4 h. A final batch of BPP (1.60 g, 0.0054 mol) and Et3N (1 ml during 5 min) were added and heating was continued for 2 h. On cooling, the mixture was extracted with Et2O (200 ml) leaving behind a gray residue. The extract was washed with H2O (2×75 ml), dried (Na2SO4) and concentrated to a black oil. The oil was dissolved in CHCl3 (12 ml), applied to a silica gel column and eluted with 5% EtOAc in hexane. After recovering the unreacted BPP, the eluting solvent was changed to 10% EtOAc in hexane. Product eluates were combined and concentrated to give 6-methoxy-4-methyl-8-(1-methyl-4-phthalimidobutylamino)-5-[5-(2-thienyl) pentoxy] quinoline as a thick orange-yellow oil, 5.57 g (87%). This material was used without further purification. was slowly added during 25 min heating was continued for 4 h heating was continued for 2 h On cooling the mixture was extracted with Et2O (200 ml) leaving behind a gray residue The extract was washed with H2O (2×75 ml) dried (Na2SO4) concentrated to a black oil The oil was dissolved in CHCl3 (12 ml) eluted with 5% EtOAc in hexane After recovering the unreacted BPP concentrated

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

Procedure: A stirred mixture of 8-amino-6-methoxy-4-methyl-5-(9-phenylnonoxy) quinoline (0.85 g, 0.002 mol) and 4-bromo-1-phthalimidopentane (BPP) (2.4 g, 0.008 mol) was heated at 125°-135° C. while Et3N (1 ml) was added in small portions during 0.5 hr. After 2 h, second portions of BPP (0.6 g) and Et3N (2 drops) were introduced. Identical additions of BPP (0.6 g) and Et3N (2 drops) were made three more times at 1 h intervals. The mixture was allowed to cool, extracted with Et2O and the extract was treated with Darco and evaporated to dryness. The residue was redissolved in Et2O (100 ml) and treated with an excess of ethereal hydrogen chloride. The resulting dark red precipitate was separated by decantation, basified with ethereal Et3N and the solvent was evaporated. The residual brown oil was dissolved in CHCl3, placed on a silica gel column (100 g) and eluted with CHCl3. Concentration of the eluate provided 0.9 g (72%) of 6-methoxy-4-methyl-8-(1-methyl-4-phthalimidobutylamino)-5-(9-phenylnonoxy) quinoline as a pale brown oil which was used without further purification. was added in small portions during 0.5 hr at 1 h to cool extracted with Et2O the extract was treated with Darco evaporated to dryness The residue was redissolved in Et2O (100 ml) treated with an excess of ethereal hydrogen chloride The resulting dark red precipitate was separated by decantation the solvent was evaporated The residual brown oil was dissolved in CHCl3 eluted with CHCl3

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

Procedure: A stirred mixture of 8-amino-6-methoxy-4-methyl-5-(9-phenylnonoxy) quinoline (0.85 g, 0.002 mol) and 4-bromo-1-phthalimidopentane (BPP) (2.4 g, 0.008 mol) was heated at 125°-135° C. while Et3N (1 ml) was added in small portions during 0.5 hr. After 2 h, second portions of BPP (0.6 g) and Et3N (2 drops) were introduced. Identical additions of BPP (0.6 g) and Et3N (2 drops) were made three more times at 1 h intervals. The mixture was allowed to cool, extracted with Et2O and the extract was treated with Darco and evaporated to dryness. The residue was redissolved in Et2O (100 ml) and treated with an excess of ethereal hydrogen chloride. The resulting dark red precipitate was separated by decantation, basified with ethereal Et3N and the solvent was evaporated. The residual brown oil was dissolved in CHCl3, placed on a silica gel column (100 g) and eluted with CHCl3. Concentration of the eluate provided 0.9 g (72%) of 6-methoxy-4-methyl-8-(1-methyl-4-phthalimidobutylamino)-5-(9-phenylnonoxy) quinoline as a pale brown oil which was used without further purification. was added in small portions during 0.5 hr at 1 h to cool extracted with Et2O the extract was treated with Darco evaporated to dryness The residue was redissolved in Et2O (100 ml) treated with an excess of ethereal hydrogen chloride The resulting dark red precipitate was separated by decantation the solvent was evaporated The residual brown oil was dissolved in CHCl3 eluted with CHCl3

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

Procedure: A stirred mixture of 8-amino-6-methoxy-4-methyl-5-(4-phenylbutoxy)quinoline (12.8 g, 0.038 mol) and 4-bromo-1-phthalimidopentane (BPP) (22.6 g., 0.076 mol) was heated at 135°-140° C. while Et3N (7 ml) was added in small portions during 1 hr. After 1.5 h at 135°-140° C., second portions of BPP (11.3 g) and Et3N (3.5 ml) were added and heating was continued for 2 h. Third portions of BPP (11.3 g) and Et3N (3.5 ml) were introduced and heating was continued for another 2 h. The mixture was allowed to cool and thoroughly extracted with Et2O (total, ca. 600 ml). The extract was treated with charcoal and then with saturated ethereal hydrogen chloride (250 ml). The resulting dark red semi-solid mass was separated by decantation and basified with ethereal Et3N. Concentration of the ethereal solution left a brown oil which was dissolved in CHCl3, placed on a silica gel column (200 g) and eluted with CHCl3. The first fractions were combined on the basis of TLC and concentrated to give 23 g of 6-methoxy-4-methyl-8-(1-methyl-4-phthalimidobutylamino)-5-(4-phenylbutoxy) quinoline as an oil which was used without further purification. was added in small portions during 1 hr heating was continued for 2 h heating was continued for another 2 h to cool thoroughly extracted with Et2O (total, ca. 600 ml) The extract was treated with charcoal The resulting dark red semi-solid mass was separated by decantation Concentration of the ethereal solution left a brown oil which was dissolved in CHCl3 eluted with CHCl3 concentrated

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

Procedure: A stirred mixture of 8-amino-6-methoxy-4-methyl-5-(4-phenylbutoxy)quinoline (12.8 g, 0.038 mol) and 4-bromo-1-phthalimidopentane (BPP) (22.6 g., 0.076 mol) was heated at 135°-140° C. while Et3N (7 ml) was added in small portions during 1 hr. After 1.5 h at 135°-140° C., second portions of BPP (11.3 g) and Et3N (3.5 ml) were added and heating was continued for 2 h. Third portions of BPP (11.3 g) and Et3N (3.5 ml) were introduced and heating was continued for another 2 h. The mixture was allowed to cool and thoroughly extracted with Et2O (total, ca. 600 ml). The extract was treated with charcoal and then with saturated ethereal hydrogen chloride (250 ml). The resulting dark red semi-solid mass was separated by decantation and basified with ethereal Et3N. Concentration of the ethereal solution left a brown oil which was dissolved in CHCl3, placed on a silica gel column (200 g) and eluted with CHCl3. The first fractions were combined on the basis of TLC and concentrated to give 23 g of 6-methoxy-4-methyl-8-(1-methyl-4-phthalimidobutylamino)-5-(4-phenylbutoxy) quinoline as an oil which was used without further purification. was added in small portions during 1 hr heating was continued for 2 h heating was continued for another 2 h to cool thoroughly extracted with Et2O (total, ca. 600 ml) The extract was treated with charcoal The resulting dark red semi-solid mass was separated by decantation Concentration of the ethereal solution left a brown oil which was dissolved in CHCl3 eluted with CHCl3 concentrated