propylthiourea

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

Procedure: A mixture of 2-bromo-1-[4-(trifluoromethyl)phenyl]ethanone (5.34 g), N-propylthiourea (2.60 g) and ethanol (50 mL) was stirred for 1 hr while heating under reflux. The reaction mixture was cooled and diluted with isopropyl ether. The precipitated solid was collected by filtration, washed with isopropyl ether and dried to give the title compound (5.11 g, yield 70%) as colorless crystals. while heating under reflux The reaction mixture was cooled The precipitated solid was collected by filtration washed with isopropyl ether dried

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

Procedure: A mixture of 2-bromo-1-[4-(trifluoromethyl)phenyl]ethanone (5.34 g), N-propylthiourea (2.60 g) and ethanol (50 mL) was stirred for 1 hr while heating under reflux. The reaction mixture was cooled and diluted with isopropyl ether. The precipitated solid was collected by filtration, washed with isopropyl ether and dried to give the title compound (5.11 g, yield 70%) as colorless crystals. while heating under reflux The reaction mixture was cooled The precipitated solid was collected by filtration washed with isopropyl ether dried

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

Procedure: A mixture of 2-bromo-1-[4-(trifluoromethyl)phenyl]ethanone (5.34 g), N-propylthiourea (2.60 g) and ethanol (50 mL) was stirred for 1 hr while heating under reflux. The reaction mixture was cooled and diluted with isopropyl ether. The precipitated solid was collected by filtration, washed with isopropyl ether and dried to give the title compound (5.11 g, yield 70%) as colorless crystals. while heating under reflux The reaction mixture was cooled The precipitated solid was collected by filtration washed with isopropyl ether dried

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

Procedure: To a solution of 2-chloroacetophenone (4.45 g, 28.8 mmol) and N-propylthiourea (3.40 g, 28.8 mmol) in ethanol (50 mL) was added sodium acetate (3.07 g, 37.4 mmol), and the mixture was heated under reflux for 1.5 hrs. Water was added to the reaction mixture, and crystals were collected by filtration. The obtained crude crystals were recrystallized from diethyl ether-hexane to give the title compound (5.64 g, 92%) as colorless crystals. the mixture was heated under reflux for 1.5 hrs were collected by filtration The obtained crude crystals were recrystallized from diethyl ether-hexane

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

Procedure: n-Propylthiourea (270 mg), 3-chloro-2-oxohexanoic acid ethyl ester (441 mg), and pyridine (0.28 ml) were added to ethanol (10 ml), and the solution was refluxed for 3.5 hours. The solvent was evaporated. The residue was extracted with chloroform (20 ml), and washed with dilute hydrochloric acid solution (10 ml). The organic layer was dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel (eluent:chloroform/methanol=100/1), 2-n-propylamino-5-n-propyl thiazole-4-carboxylic acid ethyl ester (400 mg) was obtained. the solution was refluxed for 3.5 hours The solvent was evaporated The residue was extracted with chloroform (20 ml) washed with dilute hydrochloric acid solution (10 ml) The organic layer was dried over anhydrous magnesium sulfate evaporated The residue was purified by column chromatography on silica gel (eluent:chloroform/methanol=100/1)

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

Procedure: n-Propylthiourea (270 mg), 3-chloro-2-oxohexanoic acid ethyl ester (441 mg), and pyridine (0.28 ml) were added to ethanol (10 ml), and the solution was refluxed for 3.5 hours. The solvent was evaporated. The residue was extracted with chloroform (20 ml), and washed with dilute hydrochloric acid solution (10 ml). The organic layer was dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel (eluent:chloroform/methanol=100/1), 2-n-propylamino-5-n-propyl thiazole-4-carboxylic acid ethyl ester (400 mg) was obtained. the solution was refluxed for 3.5 hours The solvent was evaporated The residue was extracted with chloroform (20 ml) washed with dilute hydrochloric acid solution (10 ml) The organic layer was dried over anhydrous magnesium sulfate evaporated The residue was purified by column chromatography on silica gel (eluent:chloroform/methanol=100/1)

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

Procedure: A solution of (Z)-6-(2-ethoxyvinyl)-8-phenyl-[1,2,4]triazolo[4,3-a]pyridine (13 mg, 0.049 mmol) in 1,4-dioxane (1 mL) and water (1 mL) was added NBS (9.4 mg, 0.054 mmol) and stirred at rt for 1 h. The mixture was then added 1-propylthiourea (6.4 mg, 0.054 mmol), heated to 85-90° C. for 10 h, then cooled and concentrated. The residue was dissolved in a mixture of 20% MeOH in dichloromethane and purified by 500 μm silica gel prep plate using 75% ethyl acetate in hexanes as an eluent. The product was collected (4.5 mg, 27.4% yield). LCMS: 336.55 (M+H), Tr 2.98 min, (Conditions A). cooled concentrated The residue was dissolved in a mixture of 20% MeOH in dichloromethane purified by 500 μm silica gel prep plate The product was collected (4.5 mg, 27.4% yield) 336.55 (M+H), Tr 2.98 min

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

Procedure: To a solution of 2-bromo-1-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)ethanone (0.346 g, 0.932 mmol) (Example 26, Step 2) in ethanol (15 mL) in a 25 mL round bottom flask was added N-propylthiourea (0.116 g, 0.979 mmol) with stirring. The resulting solution was heated to reflux for 24 hours. The reaction was cooled to room temperature and concentrated in vacuo. The residue was dissolved in methylene chloride, washed successively with Na2CO3 (10% solution) and brine, dried over Na2SO4, filtered and reconcentrated in vacuo yielding 4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)-2-(1-propylamino) thiazole as a yellow crystalline solid (0.276 g, 76%): mp 181°-182° C. 1H NMR (DMSO-d6) 400 mHz 5 7.97 (t, J=5.37 Hz, 1H), 7.78 (d, J=8.79 Hz, H), 7.42 (dd, J=5.86, 8.79, 2H), 7.37 (d, J=8.79, H), 7.15 (t, J=8.79 Hz, 2H), 3.21 (q, J=6.84, H), 3.18 (s, 3H), 1.60 (m, 2H), 0.91 (t, J=7.33, H). MS (EI): m/z 390 (M+). HRMS Δ=2.4 mmu. The resulting solution was heated to reflux for 24 hours concentrated in vacuo The residue was dissolved in methylene chloride washed successively with Na2CO3 (10% solution) and brine dried over Na2SO4 filtered

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

Procedure: A mixture of methyl 4-bromo-5-oxo-5-phenylpentanoate (5.00 g), N-propylthiourea (2.01 g) and methanol (50 ml) was refluxed for 2 hrs. The reaction solvent was removed under reduced pressure, and the residue was dissolved in ethyl acetate. The obtained solution was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give methyl 3-[4-phenyl-2-[N-(1-propyl)amino]-5-thiazolyl]propionate (3.64 g, yield 70%) as colorless crystals. The crystals were recrystallized from ethyl acetate-hexane. melting point: 67–68° C. was refluxed for 2 hrs The reaction solvent was removed under reduced pressure the residue was dissolved in ethyl acetate The obtained solution was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine dried over anhydrous magnesium sulfate concentrated