1-(isothiocyanatomethyl)-3-methoxybenzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Methoxybenzyl isothiocyanate (22 mg, 0.12 mmol) was added to a solution of 1-(RS)-[4-(3,4-dichlorobenzyl)piperazin-1-ylmethyl]-2-methylpropylamine(40 mg, 0.12 mmol) [prepared as described in Example 1 by substituting L-N-BOC-valine with DL-N-BOC-valine] in methylene chloride (1.5 ml). The reaction mixture was stirred for 2 h and then concentrated. Purification by flash chromatography with 20:1 methylene chloride: methanol as the eluant gave 1-{1-(RS)-[4-(3,4-dichlorobenzyl)piperazin-1-ylmethyl]-2-methylpropyl}-3-methoxybenzyl-2-thiourea (18 mg) as a solid. concentrated Purification by flash chromatography with 20:1 methylene chloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Methoxybenzyl isothiocyanate (22 mg, 0.12 mmol) was added to a solution of 1-(RS)-[4-(3,4-dichlorobenzyl)piperazin-1-ylmethyl]-2-methylpropylamine(40 mg, 0.12 mmol) [prepared as described in Example 1 by substituting L-N-BOC-valine with DL-N-BOC-valine] in methylene chloride (1.5 ml). The reaction mixture was stirred for 2 h and then concentrated. Purification by flash chromatography with 20:1 methylene chloride: methanol as the eluant gave 1-{1-(RS)-[4-(3,4-dichlorobenzyl)piperazin-1-ylmethyl]-2-methylpropyl}-3-methoxybenzyl-2-thiourea (18 mg) as a solid. concentrated Purification by flash chromatography with 20:1 methylene chloride

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Methoxybenzyl isothiocyanate (22 mg, 0.12 mmol) was added to a solution of 1-(RS)-[4-(3,4-dichlorobenzyl)piperazin-1-ylmethyl]-2-methylpropylamine (40 mg, 0.12 mmol) [prepared as described in Example 1 by substituting L-N-BOC-valine with DL-N-BOC-valine] in methylene chloride (1.5 ml). The reaction mixture was stirred for 2 h and then concentrated. Purification by flash chromatography with 20:1 methylene chloride:methanol as the eluant gave 1-{1-(RS)-[4-(3,4-dichlorobenzyl)piperazin-1-ylmethyl]-2-methylpropyl}-3-methoxybenzyl-2-thiourea (18 mg) as a solid. concentrated Purification by flash chromatography with 20:1 methylene chloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Methoxybenzyl isothiocyanate (22 mg, 0.12 mmol) was added to a solution of 1-(RS)-[4-(3,4-dichlorobenzyl)piperazin-1-ylmethyl]-2-methylpropylamine (40 mg, 0.12 mmol) [prepared as described in Example 1 by substituting L-N-BOC-valine with DL-N-BOC-valine] in methylene chloride (1.5 ml). The reaction mixture was stirred for 2 h and then concentrated. Purification by flash chromatography with 20:1 methylene chloride:methanol as the eluant gave 1-{1-(RS)-[4-(3,4-dichlorobenzyl)piperazin-1-ylmethyl]-2-methylpropyl}-3-methoxybenzyl-2-thiourea (18 mg) as a solid. concentrated Purification by flash chromatography with 20:1 methylene chloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Methoxybenzyl isothiocyanate (22 mg, 0.12 mmol) was added to a solution of 1-(RS)-[4-(3,4-dichlorobenzyl)piperazin-1-ylmethyl]-2-methylpropylamine (40 mg, 0.12 mmol) [prepared as described in Example 1 by substituting L-N-BOC-valine with DL-N-BOC-valine] in methylene chloride (1.5 ml). The reaction mixture was stirred for 2 h and then concentrated. Purification by flash chromatography with 20:1 methylene chloride: methanol as the eluant gave 1-{1-(RS)-[4-(3,4-dichlorobenzyl)piperazin-1-ylmethyl]-2-methylpropyl}-3-methoxybenzyl-2-thiourea (18 mg) as a solid. concentrated Purification by flash chromatography with 20:1 methylene chloride

反応条件: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Octyl amine (3.09 g, 23.9 mmol) in 83 ml ethanol at 40° C. was reacted with an excess of 3-methoxybenzyl isothiocyanate (4.7 g, 26.2 mmol) for 2 h under N2 with stirring, then transferred to a 100 ml beaker, cooled to 4° C. and the crystals filtered off using Whatman 541 filter paper. The filtrate was evaporated to 20 ml and cooled to 4° C. to obtain a second crop of crystals. The remaining supernatant was dried and weighed. The first and second crop of crystals yielded 6.32 g, or 85.5% of the theoretical amount of 1-(3-methoxybenzyl-3-octyl thiourea. Calculated elemental analysis of 1-(3-methoxybenzyl)-3-octyl thiourea: C, 66.19; H, 9.15; N, 9.08; S, 10.39. Found: C, 66.21; H, 9.04; N, 9.07; S, 10.59. the crystals filtered off filter paper The filtrate was evaporated to 20 ml cooled to 4° C. to obtain a second crop of crystals The remaining supernatant was dried

反応条件: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dodecyl amine (4.89 g, 26.4 mmol) in 83 ml ethanol at 50° C. was reacted with 3-methoxybenzyl isothiocyanate (3.97 g, 22.1 mmol) for 6 h under N2 with stirring, and then poured into a 250 ml beaker. Performing this reaction at 40° C. led to a precipitate that was difficult to stir. Crystallization began as soon as the reaction started cooling below 50° C. The reaction mixture was cooled to 4° C. and the crystals were filtered off using Whatman 54 filter paper. The crystals were washed with 15 ml of ethanol. Combined filtrates were evaporated to dryness and taken up in 10 ml ethanol. Cooling the solution to −10° C. gave no crystals. The solution was evaporated to dryness and the solids were weighed. Material recovery was 98.7%, and yield of crystals was 7.62 g, or 94.4% of the theoretical yield. Calculated elemental analysis of 1-(3-methoxybenzyl)-3-dodecyl thiourea: C, 69.18; H, 9.95; N, 7.68; S, 8.79. Found: C, 69.65; H, 10.07; N, 7.67; S, 8.80. poured into a 250 ml beaker Performing this reaction at 40° C. to stir Crystallization started cooling below 50° C the crystals were filtered off filter paper The crystals were washed with 15 ml of ethanol Combined filtrates were evaporated to dryness Cooling the solution to −10° C. gave no crystals The solution was evaporated to dryness

反応条件: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Octadecyl amine hydrochloride was converted to the amine by mixing an ether solution of the amine hydrochloride with 1 M NaOH, separating and evaporating the ether layer, dissolving the amine in CHCl3, filtering through Whatman 541 filter paper and evaporating the CHCl3. Octadecyl amine (5.9252 g, 22.0 mmol) in 150 ml ethanol was reacted with an excess (4.32 g, 24.1 mmol) of 3-methoxybenzyl isothiocyanate at 40° C. under N2 with stirring. Excess isothiocyanate was used because co-crystallization of octadecyl amine is difficult to prevent when an excess of amine is present. After 2 h the solution was cooled to 4° C., centrifuged at 10,000 rpm for 20 min and the precipitated crystals were washed with ethanol (20 ml). The combined supernatant and wash was evaporated to 20 ml total volume and then cooled to −10° C. to filter off a second batch of crystals. The supernatant was dried and 94.3% of reagents weight was recovered, 74.9%, or 7.40 g as 1-(3-methoxybenzyl)-3-(octadecyl) thiourea of about 76% purity based on the sulfur analysis. The octadecyl amine was difficult to separate from the thiourea by crystallization. Calculated elemental analysis of 1-(3-methoxybenzyl)-3-octadecyl thiourea: C, 72.27; H, 10.78; N, 6.24; S, 7.15. Found: C, 71.96; H, 11.00; N, 5.95; S, 5.46. A recrystallization from acetone/chloroform gave crystals with the composition: C, 72.37; H, 10.98; N, 6.13; S, 6.92. separating evaporating the ether layer dissolving the amine in CHCl3 filtering through Whatman 541 filter paper evaporating the CHCl3 the precipitated crystals were washed with ethanol (20 ml) The combined supernatant and wash was evaporated to 20 ml total volume cooled to −10° C. to filter off a second batch of crystals The supernatant was dried 94.3% of reagents weight was recovered to separate from the thiourea by crystallization A recrystallization from acetone/chloroform gave crystals with the composition

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The reaction of 3-methoxybenzyl isothiocyanate with 3-methoxybenzyl amine in ethanol was repeated doubling the reaction volume and reactants and heating for 2 h at 40° C. Crystallization at −10° C., followed by evaporation of the supernatant to 20 ml and a second crystallization gave 98.4% of the theoretical yield for the two crystallizations combined. Calculated elemental analysis of 3-methoxybenzyl thiourea: C, 64.53; H, 6.37; N, 8.85; S, 10.13. Found: C, 64.30; H, 6.46; N, 8.85; S, 10.09. Crystallization at −10° C. followed by evaporation of the supernatant to 20 ml a second crystallization gave 98.4% of the theoretical yield for the two crystallizations