2-(4-chlorophenyl)sulfanylbenzaldehyde

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

Procedure: To 123 mg (0.32 mmol) of (8-bromo-1-methyl-1,2,3,4-tetrahydrobenzo[e][1,4]diazepin-5-ylidenemethyl)phosphonic acid diethyl ester (prepared as described in Example 41) in 2 ml of dioxane was added 135 mg (0.38 mmol) of 2-(tributylstannyl)furan, followed by 11.1 mg (0.016 mmol) of palladium (II) bis-triphenylphosphine-dichloride. The mixture was heated at 80° C. for 18 hours. To the mixture at ambient temperature was added 55 mg (1.37 mmol) of sodium hydride (60% dispersion in mineral oil). After 5 minutes 82 mg (0.33 mmol) of 2-(4-chlorophenylthio)benzaldehyde was added and the mixture was stirred for 18 hours. The solvent was removed and the product was purified by column chromatography eluting with 24-40% acetone/petroleum ether (40-60° C.) and treated with 0.10 ml of 4M hydrogen chloride in dioxan. The solvent was evaporated and the residue was dissolved from acetone/petroleum ether (40 60° C.). The solvent was removed and the residue was recrystallised from acetone/petroleum ether (40 60° C.) to give 63 mg of (E)-5-[2-(4-chlorophenylthio)styryl]-8-(2-furyl)-2,3-dihydro-1-methyl-1H-1,4-benzodiazepine dihydrochloride as dark red crystals; MS: m/e 471 (M+). The solvent was removed the product was purified by column chromatography eluting with 24-40% acetone/petroleum ether (40-60° C.) treated with 0.10 ml of 4M hydrogen chloride in dioxan The solvent was evaporated the residue was dissolved from acetone/petroleum ether (40 60° C.) The solvent was removed the residue was recrystallised from acetone/petroleum ether (40 60° C.)

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

Procedure: To 112 mg (0.27 mmol) of [8-(3-methoxyphenyl)-1-methyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-ylidenemethyl]phosphonic acid diethyl ester (prepared as described in Example 98) in 2 ml of tetrahydrofuran was added 19 mg (0.47 mmol) of sodium hydride (60% dispersion in mineral oil). After 10 minutes 70 mg (0.28 mmol) of 2-(4-chlorophenylthio)benzaldehyde was added and the mixture was stirred for 3 hours. The product was purified by column chromatography (20 g IST pre-packed column) eluting with 1% methanol/ethyl acetate and treated with 0.10 ml of 4M hydrogen chloride in dioxan. The solvent was evaporated to leave an orange gum which was recrystallized from ethyl acetate to give 10 mg of (E)-5-[2-(4-chlorophenylthio)styryl]-2,3-dihydro-8-(3-methoxyphenyl)-1-methyl-1H-1,4-benzodiazepine dihydrochloride as a red solid; MS: m/e 510 (M+). The product was purified by column chromatography (20 g IST pre-packed column) eluting with 1% methanol/ethyl acetate treated with 0.10 ml of 4M hydrogen chloride in dioxan The solvent was evaporated to leave an orange gum which was recrystallized from ethyl acetate

Conditions: temp:22.01; pressure:0.00; stir:

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

Procedure: To 123 mg (0.32 mmol) of (8-bromo-1-methyl-1,2,3,4-tetrahydrobenzo[e][1,4]diazepin-5-ylidenemethyl)phosphonic acid diethyl ester (prepared as described in Example 41) in 2 ml of dioxane was added 135 mg (0.38 mmol) of 2-(tributylstannyl)furan, followed by 11.1 mg (0.016 mmol) of palladium (II) bis-triphenylphosphine-dichloride. The mixture was heated at 80° C. for 18 hours. To the mixture at ambient temperature was added 55 mg (1.37 mmol) of sodium hydride (60% dispersion in mineral oil). After 5 minutes 82 mg (0.33 mmol) of 2-(4-chlorophenylthio)benzaldehyde was added and the mixture was stirred for 18 hours. The solvent was removed and the product was purified by column chromatography eluting with 24-40% acetone/petroleum ether (40-60° C.) and treated with 0.10 ml of 4M hydrogen chloride in dioxan. The solvent was evaporated and the residue was dissolved from acetone/petroleum ether (40 60° C.). The solvent was removed and the residue was recrystallised from acetone/petroleum ether (40 60° C.) to give 63 mg of (E)-5-[2-(4-chlorophenylthio)styryl]-8-(2-furyl)-2,3-dihydro-1-methyl-1H-1,4-benzodiazepine dihydrochloride as dark red crystals; MS: m/e 471 (M+). The solvent was removed the product was purified by column chromatography eluting with 24-40% acetone/petroleum ether (40-60° C.) treated with 0.10 ml of 4M hydrogen chloride in dioxan The solvent was evaporated the residue was dissolved from acetone/petroleum ether (40 60° C.) The solvent was removed the residue was recrystallised from acetone/petroleum ether (40 60° C.)

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

Procedure: To 112 mg (0.27 mmol) of [8-(3-methoxyphenyl)-1-methyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-ylidenemethyl]phosphonic acid diethyl ester (prepared as described in Example 98) in 2 ml of tetrahydrofuran was added 19 mg (0.47 mmol) of sodium hydride (60% dispersion in mineral oil). After 10 minutes 70 mg (0.28 mmol) of 2-(4-chlorophenylthio)benzaldehyde was added and the mixture was stirred for 3 hours. The product was purified by column chromatography (20 g IST pre-packed column) eluting with 1% methanol/ethyl acetate and treated with 0.10 ml of 4M hydrogen chloride in dioxan. The solvent was evaporated to leave an orange gum which was recrystallized from ethyl acetate to give 10 mg of (E)-5-[2-(4-chlorophenylthio)styryl]-2,3-dihydro-8-(3-methoxyphenyl)-1-methyl-1H-1,4-benzodiazepine dihydrochloride as a red solid; MS: m/e 510 (M+). The product was purified by column chromatography (20 g IST pre-packed column) eluting with 1% methanol/ethyl acetate treated with 0.10 ml of 4M hydrogen chloride in dioxan The solvent was evaporated to leave an orange gum which was recrystallized from ethyl acetate

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

Procedure: To a solution of 2-(4-chlorophenylthio)benzaldehyde (2.00 g, 8.00 mmol) in dichloromethane (20 mL) at 0° C. was added meta chloroperoxybenzoic acid (77% max, 5.40 g, 24.17 mmol) in, portions over 15 minutes, then warmed to room temperature and stirred for 2 hours. Aqueous sodium metabisulfite solution was added carefully until effervescence ceased. This solution was extracted with dichloromethane and the combined organic extracts were washed with NaOH (1N) then saturated brine, dried over MgSO4 and concentrated in vacuo giving a white solid (1.05 g, 3.74 mmol, 46%). δH (300 MHz, d6-DMSO) 10.69 (1H, s, CHO), 8.25-8.18 (1H, m, Ar), 8.07-8.00 (2H, m, Ar), 8.00-7.90 (3H, m, Ar) and 7.81-7.64 (3H, m, Ar). This solution was extracted with dichloromethane the combined organic extracts were washed with NaOH (1N) saturated brine, dried over MgSO4 concentrated in vacuo

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

Procedure: To a solution of 2-(4-chlorophenylthio)benzaldehyde (2.00 g, 8.00 mmol) in dichloromethane (20 mL) at 0° C. was added meta chloroperoxybenzoic acid (77% max, 5.40 g, 24.17 mmol) in, portions over 15 minutes, then warmed to room temperature and stirred for 2 hours. Aqueous sodium metabisulfite solution was added carefully until effervescence ceased. This solution was extracted with dichloromethane and the combined organic extracts were washed with NaOH (1N) then saturated brine, dried over MgSO4 and concentrated in vacuo giving a white solid (1.05 g, 3.74 mmol, 46%). δH (300 MHz, d6-DMSO) 10.69 (1H, s, CHO), 8.25-8.18 (1H, m, Ar), 8.07-8.00 (2H, m, Ar), 8.00-7.90 (3H, m, Ar) and 7.81-7.64 (3H, m, Ar). This solution was extracted with dichloromethane the combined organic extracts were washed with NaOH (1N) saturated brine, dried over MgSO4 concentrated in vacuo

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

Procedure: To a solution of 2-(4-chlorophenylthio)benzaldehyde (2.00 g, 8.00 mmol) in dichloromethane (20 mL) at 0° C. was added meta chloroperoxybenzoic acid (77% max, 5.40 g, 24.17 mmol) in portions over 15 minutes, then warmed to room temperature and stirred for 2 hours. Aqueous sodium metabisulfite solution was added carefully until effervescence ceased. This solution was extracted with dichloromethane and the combined organic extracts were washed with NaOH (1N) then saturated brine, dried over MgSO4 and concentrated in vacuo giving a white solid (1.05 g, 3.74 mmol, 46%). δH (300 MHz, d6-DMSO) 10.69 (1H, s, CHO), 8.25-8.18 (1H, m, Ar), 8.07-8.00 (2H, m, Ar), 8.00-7.90 (3H, m, Ar) and 7.81-7.64 (3H, m, Ar). This solution was extracted with dichloromethane the combined organic extracts were washed with NaOH (1N) saturated brine, dried over MgSO4 concentrated in vacuo

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

Procedure: To 123 mg (0.32 mmol) of (8-bromo-1-methyl-1,2,3,4-tetrahydrobenzo[e][1,4]diazepin-5-ylidenemethyl)phosphonic acid diethyl ester (prepared as described in Example 41) in 2 ml of dioxane was added 135 mg (0.38 mmol) of 2-(tributylstannyl)furan, followed by 11.1 mg (0.016 mmol) of palladium (II) bis-triphenylphosphine-dichloride. The mixture was heated at 80° C. for 18 hours. To the mixture at ambient temperature was added 55 mg (1.37 mmol) of sodium hydride (60% dispersion in mineral oil). After 5 minutes 82 mg (0.33 mmol) of 2-(4-chlorophenylthio)benzaldehyde was added and the mixture was stirred for 18 hours. The solvent was removed and the product was purified by column chromatography eluting with 24-40% acetone/petroleum ether (40-60° C.) and treated with 0.10 ml of 4M hydrogen chloride in dioxan. The solvent was evaporated and the residue was dissolved from acetone/petroleum ether (40 60° C.). The solvent was removed and the residue was recrystallised from acetone/petroleum ether (40 60° C.) to give 63 mg of (E)-5-[2-(4-chlorophenylthio)styryl]-8-(2-furyl)-2,3-dihydro-1-methyl-1H-1,4-benzodiazepine dihydrochloride as dark red crystals; MS: m/e 471 (M+). The solvent was removed the product was purified by column chromatography eluting with 24-40% acetone/petroleum ether (40-60° C.) treated with 0.10 ml of 4M hydrogen chloride in dioxan The solvent was evaporated the residue was dissolved from acetone/petroleum ether (40 60° C.) The solvent was removed the residue was recrystallised from acetone/petroleum ether (40 60° C.)

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

Procedure: To 112 mg (0.27 mmol) of [8-(3-methoxyphenyl)-1-methyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-ylidenemethyl]phosphonic acid diethyl ester (prepared as described in Example 98) in 2 ml of tetrahydrofuran was added 19 mg (0.47 mmol) of sodium hydride (60% dispersion in mineral oil). After 10 minutes 70 mg (0.28 mmol) of 2-(4-chlorophenylthio)benzaldehyde was added and the mixture was stirred for 3 hours. The product was purified by column chromatography (20 g IST pre-packed column) eluting with 1% methanol/ethyl acetate and treated with 0.10 ml of 4M hydrogen chloride in dioxan. The solvent was evaporated to leave an orange gum which was recrystallized from ethyl acetate to give 10 mg of (E)-5-[2-(4-chlorophenylthio)styryl]-2,3-dihydro-8-(3-methoxyphenyl)-1-methyl-1H-1,4-benzodiazepine dihydrochloride as a red solid; MS: m/e 510 (M+). The product was purified by column chromatography (20 g IST pre-packed column) eluting with 1% methanol/ethyl acetate treated with 0.10 ml of 4M hydrogen chloride in dioxan The solvent was evaporated to leave an orange gum which was recrystallized from ethyl acetate