N-butyl-N-(3-chloropropyl)butan-1-amine

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 mixture of 3-(4-hydroxybenzoyl)-8-methylimidazo[1,2-a]pyridine (2.3 g, 9.6 mmol), dibutylaminopropyl chloride (6.8 g, 33 mmol) and potassium hydroxide (1.3 g, 23 mmol) in methanol (60 ml) was stirred at reflux for 96 hours. The mixture was concentrated and the resulting oil was flash chromatographed (silica gel, 2.5% methanol in diethyl ether) to give 1.3 g (31% yield) of the free base of the title compound. The HCl salt was prepared by dropwise addition of concentrated hydrochloric acid to a solution of the free base in methanol, concentrated and recrystallized from acetone-ether to give the HCl salt of the title compound as an off-white solid, mp 105° C. to 107° C. IR(KBr): 3440, 2640, 1645, 1605 cm-1. MS: 421 (M+). 1H NMR (CD3OD): δ9.66 (d, J=8 Hz, 1H), 8.74 (s, 1H), 8.00-7.61 (m, 4H), 7.20 (d, J=7.2 Hz, 2H), 4.29 (t, J=5 Hz, 2H), 3.41-3.15 (m, 6H), 2.75 (s, 3H), 2.31 (m, 2H), 1.80-1.42 (m, 8H), 1.02 (m, 6H). at reflux for 96 hours The mixture was concentrated chromatographed (silica gel, 2.5% methanol in diethyl ether)

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

Procedure: Industrial application of this last reaction step involves difficulties, because 2-n-butyl-3-(4-methoxybenzoyl)-5-nitro-benzofuran (X) is mutagenic, and aluminum chloride is harmful for the health. The resulting 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitro-benzofuran (XI) on reaction with dibutylamino-propylchloride furnishes 2-n-butyl-3-[4-(3-dibutylamino-propoxy)benzoyl]-5-nitro-benzofuran (XII) Industrial application of this last reaction step

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

Procedure: A mixture of 2.0 g. (6.4 mmol.) of 3-(4-hydroxybenzoyl)-2-phenylbenzofuran, 1.3 g. (6.4 mmol.) of 3-di-n-butylaminopropyl chloride and 4.0 g. (0.04 mol.) of anhydrous potassium carbonate in 20 ml. of dry 2-butanone is refluxed for 18 hours. The reaction is cooled, water and ether are added and the layers are separated. The organic phase is extracted with 10% aqueous sodium hydroxide and the aqueous layers are combined and extracted again with water. The combined ether extracts are concentrated under reduced pressure to give the title compound. A mixture of 2.0 g The reaction is cooled the layers are separated The organic phase is extracted with 10% aqueous sodium hydroxide extracted again with water The combined ether extracts are concentrated under reduced pressure

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

Procedure: A mixture of 2.0 g. (6.4 mmol.) of 3-(4-hydroxybenzoyl)-2-phenylbenzofuran, 1.3 g. (6.4 mmol.) of 3-di-n-butylaminopropyl chloride and 4.0 g. (0.04 mol.) of anhydrous potassium carbonate in 20 ml. of dry 2-butanone is refluxed for 18 hours. The reaction is cooled, water and ether are added and the layers are separated. The organic phase is extracted with 10% aqueous sodium hydroxide and the aqueous layers are combined and extracted again with water. The combined ether extracts are concentrated under reduced pressure to give the title compound. A mixture of 2.0 g The reaction is cooled the layers are separated The organic phase is extracted with 10% aqueous sodium hydroxide extracted again with water The combined ether extracts are concentrated under reduced pressure

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

Procedure: A solution of 0.014 mol of 4-(4-hydroxy-phenylthio) pyridine and 3 g of finely crushed anhydrous potassium carbonate in 50 ml of dimethylsulphoxide was placed under stirring for 30 min. To this medium 0.016 mol of 1-chloro-3-(di-n-butylamino) propane was added and the stirring was maintained at room-temperature for 24 hours. The reaction medium was poured into water and extracted with ethyl ether. The organic phase was washed with water, dried on sodium sulphate and filtered. After the solvent was evaporated off, an oil was provided which was purified by chromatography on a silica column (eluent:methanol). The required compound in free base form so obtained was then transformed into an oxalate by adding an ethereal solution of oxalic acid. the stirring was maintained at room-temperature for 24 hours extracted with ethyl ether The organic phase was washed with water dried on sodium sulphate filtered After the solvent was evaporated off an oil was provided which was purified by chromatography on a silica column (eluent:methanol)

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

Procedure: A solution of 0.014 mol of 4-(4-hydroxy-phenylthio) pyridine and 3 g of finely crushed anhydrous potassium carbonate in 50 ml of dimethylsulphoxide was placed under stirring for 30 min. To this medium 0.016 mol of 1-chloro-3-(di-n-butylamino) propane was added and the stirring was maintained at room-temperature for 24 hours. The reaction medium was poured into water and extracted with ethyl ether. The organic phase was washed with water, dried no sodium sulphate and filtered. After the solvent was evaporated off, an oil was provided which was purified by chromatography on a silica column (eluent: methanol). The required compound in free base form so obtained was then transformed into an oxalate by adding an ethereal solution of oxalic acid. the stirring was maintained at room-temperature for 24 hours extracted with ethyl ether The organic phase was washed with water dried no sodium sulphate filtered After the solvent was evaporated off an oil was provided which was purified by chromatography on a silica column (eluent: methanol)

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

Procedure: A solution of 0.014 mol of 4-(4-hydroxy-phenylthio) pyridine and 3 g of finely crushed anhydrous potassium carbonate in 50 ml of dimethylsulphoxide was placed under stirring for 30 min. To this medium 0.016 mol of 1-chloro-3-(di-n-butylamino) propane was added and the stirring was maintained at room-temperature for 24 hours. The reaction medium was poured into water and extracted with ethyl ether. The organic phase was washed with water, dried no sodium sulphate and filtered. After the solvent was evaporated off, an oil was provided which was purified by chromatography on a silica column (eluent: methanol). The required compound in free base form so obtained was then transformed into an oxalate by adding an ethereal solution of oxalic acid. the stirring was maintained at room-temperature for 24 hours extracted with ethyl ether The organic phase was washed with water dried no sodium sulphate filtered After the solvent was evaporated off an oil was provided which was purified by chromatography on a silica column (eluent: methanol)

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

Procedure: As in Example 14, Stage B, 14.5 g. (0.06 mol) of 4-hydroxy-3-phenyl-5,6,7,8-tetrahydrocoumarin are caused to react with 16.2 g. (0.078 mol) of 1-chloro-3-dibutylaminopropane. 19.8 g. of an oil which cannot be crystallised are obtained. Yield 80.5% (theoretical yield 24.6 g.). to react with 16.2 g of an oil which cannot be crystallised are obtained

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

Procedure: As in Example 14, Stage B, 14.5 g. (0.06 mol) of 4-hydroxy-3-phenyl-5,6,7,8-tetrahydrocoumarin are caused to react with 16.2 g. (0.078 mol) of 1-chloro-3-dibutylaminopropane. 19.8 g. of an oil which cannot be crystallised are obtained. Yield 80.5% (theoretical yield 24.6 g.). to react with 16.2 g of an oil which cannot be crystallised are obtained

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

Procedure: 1.68 g of 2-butyl-3-(4-hydroxybenzoyl)-5-hydroxymethyl-1-benzofuran, 1.18 g of 1-chloro-3-(dibutylamino)propane and 0.960 g of potassium carbonate are dissolved in 70 ml of methyl ethyl ketone. The mixture is brought to reflux for 6 hours, water is added and separation is carried out by settling. Extraction with ethyl acetate and washing with a saturated sodium chloride solution are carried out. Purification is subsequently carried out by chromatography on silica (eluent: 95/5 dichloromethane/methanol), which gives the desired compound in the free base form. to reflux for 6 hours separation Extraction with ethyl acetate washing with a saturated sodium chloride solution Purification