1,3-dicyclohexylthiourea

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 N,N'-dicyclohexylthiourea (10.0 g, 42 mmoles) and dimethylacetylenedicarboxylate (7.8 g, 55 mmoles) in methanol (100 mls) is stirred at room temperature for 16 hours, then warmed on a steambath for 45 minutes and cooled. The precipitate is filtered off, rinsed with cold methanol and dried. This gave the product as white crystals, (11.3 g), mp 97°-98° C. warmed on a steambath for 45 minutes cooled The precipitate is filtered off rinsed with cold methanol dried

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

Procedure: N-(4-Phenoxybutyl)-N'-3-pyridylthiourea (1.41 g) was dissolved in acetonitrile (10 ml), and cyanamide (400 mg), N,N'dicyclohexylcarbodiimide (1.95 g) and triethylamine (0.08 ml) were added. The mixture was stirred for 3 days at room temperature, when it was filtered, washed with acetonitrile, and ether to yield a solid mixture of the crude product and N,N'-dicyclohexylthiourea. The pure compound was obtained by extracting the mixture with 0.5N hydrochloric acid (16 ml), filtering and re-precipitation by addition of 9N sodium hydroxide to the filtrate. when it was filtered washed with acetonitrile, and ether to yield The pure compound was obtained by extracting the mixture with 0.5N hydrochloric acid (16 ml) filtering re-precipitation by addition of 9N sodium hydroxide to the filtrate

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

Procedure: N-(4-Phenoxybutyl)-N'-3-pyridylthiourea (1.41 g) was dissolved in acetonitrile (10 ml), and cyanamide (400 mg), N,N'dicyclohexylcarbodiimide (1.95 g) and triethylamine (0.08 ml) were added. The mixture was stirred for 3 days at room temperature, when it was filtered, washed with acetonitrile, and ether to yield a solid mixture of the crude product and N,N'-dicyclohexylthiourea. The pure compound was obtained by extracting the mixture with 0.5N hydrochloric acid (16 ml), filtering and re-precipitation by addition of 9N sodium hydroxide to the filtrate. when it was filtered washed with acetonitrile, and ether to yield The pure compound was obtained by extracting the mixture with 0.5N hydrochloric acid (16 ml) filtering re-precipitation by addition of 9N sodium hydroxide to the filtrate

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 5-aminoisoquinoline (14.4 g.) in pyridine (40 cc.) is added dropwise to a solution of triethylamine (10.1 g.) and carbon disulphide (40 cc.) in pyridine (20 cc.), whilst stirring at a temperature of about -10° C. After 1 hour at this temperature, a solution of N,N'-dicyclohexylcarbodiimide (20.6 g.) in pyridine (20 cc.) is added dropwise. Stirring is continued for 3 hours at a temperature changing from -10° to 20° C . and then for 20 hours at a temperature of about 20° C. The N,N'-dicyclohexylthiourea formed is filtered off and washed with methylene chloride (50 cc.); the filtrate is evaporated to dryness under reduced pressure (20 mm. Hg) at 40° C. The solid residue is taken up in methylene chloride (100 cc.); the new insoluble material is filtered off and washed with methylene chloride (30 cc.); the filtrate is evaporated to dryness under reduced pressure (20 mm. Hg) at 40° C. The residue is dissolved in boiling acetonitrile (100 cc.); after cooling, the crystals formed are filtered off and then suspended in diisopropyl ether (180 cc.). After 30 minutes'stirring at a temperature of about 20° C, the insoluble material is filtered off. The filtrate is evaporated to dryness under reduced pressure (20 mm. Hg) at 50° C. The residue is crystalline beige solid (5.9 g.) consisting of 5-isothiocyanatoisoquinoline, melting at 99° C. after recrystallisation from acetonitrile (40 cc.) and at 102° C. after sublimation at 70° C under reduced pressure (1 mm. Hg). Stirring is continued for 3 hours at a temperature changing from -10° to 20° C and then for 20 hours at a temperature of about 20° C

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

Procedure: 5.2 g of 2,4'-dichloro-3'-sulfamoylacetophenone and 4.8 g of 1,3-dicyclohexylthiourea were reacted according to the prescription made in Example 12, the end product was precipitated with 200 ml of diethyl ether and the oil was crystallized after decanting the solvent with diethyl ether. Colorless, crystalline solid body: melting point: 177° C (from acrylonitrile). the end product was precipitated with 200 ml of diethyl ether the oil was crystallized after decanting the solvent with diethyl ether

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

Procedure: 2.4 g of 1,3-dicyclohexyl-thiourea were added to 3,5 g of 2-bromo-2',4'-dichloro-5'-sulfamoylacetophenone in 40 ml of ethyl acetate. The whole was allowed to stand overnight at 20° C, the crystals were filtered off and washed with ethyl acetate. M.p. 161°-163° C. the crystals were filtered off washed with ethyl acetate

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

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

Procedure: N-(4-Phenoxybutyl)-N'-3-pyridylthiourea (1.41 g) was dissolved in acetonitrile (10 ml), and cyanamide (400 mg), N,N'dicyclohexylcarbodiimide (1.95 g) and triethylamine (0.08 ml) were added. The mixture was stirred for 3 days at room temperature, when it was filtered, washed with acetonitrile, and ether to yield a solid mixture of the crude product and N,N'-dicyclohexylthiourea. The pure compound was obtained by extracting the mixture with 0.5N hydrochloric acid (16 ml), filtering and re-precipitation by addition of 9N sodium hydroxide to the filtrate. when it was filtered washed with acetonitrile, and ether to yield The pure compound was obtained by extracting the mixture with 0.5N hydrochloric acid (16 ml) filtering re-precipitation by addition of 9N sodium hydroxide to the filtrate

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

Procedure: 5.2 g of 2,4'-dichloro-3'-sulfamoylacetophenone and 4.8 g of 1,3-dicyclohexylthiourea were reacted according to the prescription made in Example 12, the end product was precipitated with 200 ml of diethyl ether and the oil was crystallized after decanting the solvent with diethyl ether. Colorless, crystalline solid body: melting point: 177° C. (from acrylonitrile). the end product was precipitated with 200 ml of diethyl ether the oil was crystallized after decanting the solvent with diethyl ether

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

Procedure: A mixture of 2.4 gm. (0.01 mole) of N,N'-dicyclohexylthiourea, 3.15 gm. (0.012 mole) of triphenylphosphine, 1.55 gm. (0.01 mole) of carbon tetrachloride, and 1.0 gm. (0.01 mole) of triethylamine in 25 ml. of methylene chloride is stirred for 2.5 hr. at 40°-45°. The reaction mixture is concentrated and the residue extracted several times with hot Skellysolve B. The combined Skellysolve B extracts are cooled to room temperature, filtered and evaporated. The crude N,N'-dicyclohexylcarbodiimide is reacted with 5 ml. of morpholine in 10 ml of tert-butyl alcohol at reflux for 16 hours. The reaction mixture is evaporated, toluene added and concentrated to remove residual morpholine. The residue is partitioned between ether and 10% hydrochloric acid. The acid layer is basified with 20% sodium hydroxide solution, nitrogen bubbled through the solution to remove ether and cooled at 5°. The product is collected, 2.07 gm. (70%), m.p. 105°-107°. The HCl salt is prepared and recrystallized from acetonitrile-ether, m.p. 226°-227°. A mixture of 2.4 gm at 40°-45° The reaction mixture is concentrated the residue extracted several times with hot Skellysolve B filtered evaporated The crude N,N'-dicyclohexylcarbodiimide is reacted with 5 ml The reaction mixture is evaporated toluene added concentrated to remove residual morpholine The residue is partitioned between ether and 10% hydrochloric acid bubbled through the solution to remove ether cooled at 5° The product is collected recrystallized from acetonitrile-ether, m.p. 226°-227°

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

Procedure: 2.44 g of N-[4 -(β-<2-methoxy-5-methyl-benzamido>-ethyl)-benzenesulfonyl]-N'-cyclopentyl-methyl-thio-urea (I) were dissolved together with 1.03 g of dicyclohexylcarbodiimide in 20 ml of hot dioxane. The whole was allowed to cool and to stand for several days. Thereupon, the N,N'-dicyclohexyl-thiourea that had formed (melting point 176° - 178° C) was filtered off with suction. The filtrate which contained the N-[4-(β-<2-methoxy-5-methyl-benzamido>ethyl)-benzenesulfonyl]-N'-cyclopentyl-methyl-carbodiimide (II) in dissolved state, was combined with about 5 ml of water. The whole was shortly heated on a water bath and concentrated. The residue was dissolved in a mixture of toluene, ether and dilute aqueous ammonia, while shaking. The aqueous phase was separated. The toluene/ether phase was extracted again with dilute ammonia. The aqueous extracts were united and acidified. There was obtained a precipitate, constituting the N-[4-(β-<2-methoxy-5-methyl-benzamido>-ethyl)-benzenesulfonyl]-N'-cyclopentylmethylurea (III). After recrystallization from methanol, the sulfonylurea was found to melt at 148° - 150° C. to cool to stand for several days