N-(3-aminopropyl)benzamide

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

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

Procedure: Triethylamine (9.3 mL, 67 mmol) was added to a mixture of 4-chloro-3-nitroquinoline hydrochloride (16.4 g, 67 mmol) and dichloromethane (400 mL). A solution of N-(3-aminopropyl)benzamide (11.9 g, 67 mmol) in dichloromethane (100 mL) was added all a once. The reaction mixture was stirred at ambient temperature for 1 hour and then heated on a steam bath for 1 hour. The resulting precipitate was isolated by filtration to provide 6 g of N1-{3-[(3-nitroquinolin-4-yl)amino]propyl}benzamide as a yellow solid, m.p. 209-211° C. 1H NMR (500 MHz, DMSO-d6) δ 9.07 (broad s, 1H), 9.05 (s, 1H), 8.54 (t, J=6.0 Hz, 1H), 8.51 (d, J=8.0 Hz, 1H), 7.89 (d, J=8.0 Hz, 1H), 7.82 (t, J=8.0 Hz, 1H), 7.76 (d, J=8.0 Hz, 2H), 7.55 (t, J=8.0 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 7.43 (t, J=8.0 Hz, 2H), 3.69 (q, J=6.0 Hz, 2H), 3.35 (q, J=6.0 Hz, 2H), 2.00 (quintet, J=7.0 Hz, 2H). heated on a steam bath for 1 hour The resulting precipitate was isolated by filtration

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzamide (25 g, 0.20 mol) and 1,3-diaminopropane (45.9 g, 0.60 mol) were combined in a Parr vessel and heated to 150° C. for 15 hours. The vessel was cooled and the reaction mixture was concentrated under vacuum to remove excess diamine. The residue was dissolved in water (500 mL) and concentrated hydrochloric acid was added to adjust the pH to <1. The resulting precipitate (starting benzamide and diacylated product) was removed by filtration. The filtrate was washed with dichloromethane. The aqueous layer was made strongly basic by the addition of 50% sodium hydroxide and then it was extracted with dichloromethane (4×300 mL). The extracts were combined, washed with brine (300 mL), dried over sodium sulfate and then concentrated under vacuum to provide 11.9 g of N-(3-aminopropyl)benzamide as an oil. The vessel was cooled the reaction mixture was concentrated under vacuum to remove excess diamine The residue was dissolved in water (500 mL) concentrated hydrochloric acid was added The resulting precipitate (starting benzamide and diacylated product) was removed by filtration The filtrate was washed with dichloromethane The aqueous layer was made strongly basic by the addition of 50% sodium hydroxide it was extracted with dichloromethane (4×300 mL) washed with brine (300 mL) dried over sodium sulfate concentrated under vacuum

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

Procedure: 1-Nitro-2-methylthio-2-[2-((5-methyl-4-imidazolyl)methylthio)ethylamino]ethylene was reacted with 3-benzoylaminopropylamine and the product was hydrolyzed under acidic conditions and reacted with N-cyano-N'-[2-(2-pyridylmethylthio)ethyl]-S-methylisothiourea to give the title compound.

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

Procedure: i. 3-Benzoylaminopropylamine was treated successively with carbon disulphide and methyl iodide according to the general procedure of Example 1(a)(b) to give S-methyl-N-(3-benzoylaminopropyl)dithiocarbamate hydriodide

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

Procedure: Triethylamine (9.3 mL, 67 mmol) was added to a mixture of 4-chloro-3-nitroquinoline hydrochloride (16.4 g, 67 mmol) and dichloromethane (400 mL). A solution of N-(3-aminopropyl)benzamide (11.9 g, 67 mmol) in dichloromethane (100 mL) was added all a once. The reaction mixture was stirred at ambient temperature for 1 hour and then heated on a steam bath for 1 hour. The resulting precipitate was isolated by filtration to provide 6 g of N1-{3-[(3-nitroquinolin-4-yl)amino]propyl}benzamide as a yellow solid, m.p. 209-211° C. 1H NMR (500 MHz, DMSO-d6) δ 9.07 (broad s, I—H), 9.05 (s, 1H), 8.54 (t, J=6.0 Hz, 1H), 8.51 (d, J=8.0 Hz, 1H), 7.89 (d, J=8.0 Hz, 1H), 7.82 (t, J=8.0 Hz, 1H), 7.76 (d, J=8.0 Hz, 2H), 7.55 (t, J=8.0 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 7.43 (t, J=8.0 Hz, 2H), 3.69 (q, J=6.0 Hz, 2H), 3.35 (q, J=6.0 Hz, 2H), 2.00 (quintet, J=7.0 Hz, 2H). heated on a steam bath for 1 hour The resulting precipitate was isolated by filtration

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzamide (25 g, 0.20 mol) and 1,3-diaminopropane (45.9 g, 0.60 mol) were combined in a Parr vessel and heated to 150° C. for 15 hours. The vessel was cooled and the reaction mixture was concentrated under vacuum to remove excess diamine. The residue was dissolved in water (500 mL) and concentrated hydrochloric acid was added to adjust the pH to <1. The resulting precipitate (starting benzamide and diacylated product) was removed by filtration. The filtrate was washed with dichloromethane. The aqueous layer was made strongly basic by the addition of 50% sodium hydroxide and then it was extracted with dichloromethane (4×300 mL). The extracts were combined, washed with brine (300 mL), dried over sodium sulfate and then concentrated under vacuum to provide 11.9 g of N-(3-aminopropyl)benzamide as an oil. The vessel was cooled the reaction mixture was concentrated under vacuum to remove excess diamine The residue was dissolved in water (500 mL) concentrated hydrochloric acid was added The resulting precipitate (starting benzamide and diacylated product) was removed by filtration The filtrate was washed with dichloromethane The aqueous layer was made strongly basic by the addition of 50% sodium hydroxide it was extracted with dichloromethane (4×300 mL) washed with brine (300 mL) dried over sodium sulfate concentrated under vacuum

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

Procedure: 1-Nitro-2-methylthio-2-[2-((5-methyl-4-imidazolyl)methylthio)ethylamino]ethylene was reacted with 3-benzoylaminopropylamine and the product was hydrolysed under acidic conditions and reacted with N-cyano-N'[2-(2-pyridylmethylthio)ethyl]-S-methylisothiourea to give the title compound.

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

Procedure: (i) 3-Benzoylaminopropylamine was treated successively with carbon disulphide and methyl iodide according to the general procedure of Example 1 (a) (b) to give S-methyl-N-(3-benzoylaminopropyl)dithiocarbamate hydriodide

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

Procedure: 1-Nitro-2-methylthio-2-[2-((5-methyl-4-imidazolyl)methylthio)ethylamino]ethylene was reacted with 3-benzoylaminopropylamine and the product was hydrolysed under acidic conditions and reacted with N-cyano-N'-[2-(2-pyridylmethylthio)ethyl]-S-methylisothiourea to give the title compound.

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

Procedure: 1-Nitro-2-methylthio-2-[2-((5-methyl-4-imidazolyl)methylthio)ethylamino]ethylene was reacted with 3-benzoylaminopropylamine and the product was hydrolysed under acidic conditions and reacted with N-cyano-N'-[2-(2-pyridylmethylthio)ethyl]-S-methylisothiourea to give the title compound.

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

Procedure: (i) 3-Benzoylaminopropylamine was treated successively with carbon disulphide and methyl iodide according to the general procedure of Example 1(a) (b) to give S-methyl-N-(3-benzoylaminopropyl)dithiocarbamate hydriodide