4,5-dihydro-1,3-thiazol-2-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:

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: To a stirred and refluxing solution of 3.06 parts of 2-amino-2-thiazoline in 60 parts of dioxane is added a solution of 4.2 parts of p-(2-thenoyl)hydratropoyl chloride in 45 parts of dioxane. Upon completion, stirring at reflux is continued for 30 minutes. The reaction mixture is cooled, filtered and the filtrate is evaporated. The residue is purified by column-chromatography over silicagel, using a mixture of chloroform and 5% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from ethanol, yielding N-(2-thiazolin-2-yl)-p-(2-thenoyl)hydratropamide; mp. 186.4° C. Upon completion, stirring at reflux The reaction mixture is cooled filtered the filtrate is evaporated The residue is purified by column-chromatography over silicagel a mixture of chloroform and 5% of methanol as eluent The pure fractions are collected the eluent is evaporated The residue is crystallized from ethanol

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

Procedure: To a stirred and refluxing solution of 3.06 parts of 2-amino-2-thiazoline in 60 parts of dioxane is added a solution of 4.2 parts of p-(2-thenoyl)hydratropoyl chloride in 45 parts of dioxane. Upon completion, stirring at reflux is continued for 30 minutes. The reaction mixture is cooled, filtered and the filtrate is evaporated. The residue is purified by column-chromatography over silicagel, using a mixture of chloroform and 5% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from ethanol, yielding N-(2-thiazolin-2-yl)-p-(2-thenoyl)hydratropamide; mp. 186.4° C. Upon completion, stirring at reflux The reaction mixture is cooled filtered the filtrate is evaporated The residue is purified by column-chromatography over silicagel a mixture of chloroform and 5% of methanol as eluent The pure fractions are collected the eluent is evaporated The residue is crystallized from ethanol

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

Procedure: A mixture of 51.6 g (0.3 mol) of 4-fluorophenacylchloride, 33.66 g (0.33 mol) of 2-aminothiazoline and 200 ml of ethanol was heated at reflux for 2 hours. The mixture was cooled to room temperature at which point 300 ml of water was added. After a reflux period of 2 hours, the mixture was concentrated to remove about 190 ml of aqueous alcohol. The pH of the residue was adjusted to about 2 with 10% hydrochloric acid (10 ml). The solid product was separated and dried to give 65.4 g (85%) of 6-(4-fluorophenyl)-2,3-dihydroimidazo[2,1-b]thiazole, m.p. 116-118°. was heated at reflux for 2 hours was added the mixture was concentrated to remove about 190 ml of aqueous alcohol The solid product was separated dried

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

Procedure: In 300 ml of methyl ethyl ketone was dissolved 10.2 g of 2-amino-2-thiazoline and after adding 32.7 g of 3,5-di-tert-butyl-4-hydroxyphenacyl bromide was added portionwise to the solution followed by stirring for 30 minutes at room temperature, the resultant mixture was refluxed for one hour. Then, the solvent was distilled off under reduced pressure, the crystals thus formed were dissolved in 200 ml of ethanol, and the solution was refluxed for 4 hours. The reaction mixture was basified with the addition of aqueous ammonia and then 200 ml of water was added to the reaction mixture to precipitate crude crystals, which were recovered by filtration and recrystallized from ethanol to provide 23.5 g of 6-(3,5-di-tert-butyl-4-hydroxyphenyl)-2,3-dihydroimidazo[2,1-b]thiazole. was added portionwise to the solution Then, the solvent was distilled off under reduced pressure the crystals thus formed the solution was refluxed for 4 hours to precipitate crude crystals, which were recovered by filtration recrystallized from ethanol

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

Procedure: 50 mg of 3-chloro-4-(4-chloro-3-(pyridin-2-yl)phenylcarbamoyl)benzoic acid was coupled to 2-amino-4,5-dihydrothiazole via Procedure G. The product was purified on reverse phase HPLC to yield 2-chloro-N1-(4-chloro-3-(pyridin-2-yl)phenyl)-N4-(4,5-dihydrothiazol-2-yl)terephthalamide. MS (Q1) 471 (M)+. The product was purified on reverse phase HPLC

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

Procedure: 50 mg of 3-chloro-4-(4-chloro-3-(pyridin-2-yl)phenylcarbamoyl)benzoic acid was coupled to 2-amino-4,5-dihydrothiazole via Procedure G. The product was purified on reverse phase HPLC to yield 2-chloro-N1-(4-chloro-3-(pyridin-2-yl)phenyl)-N4-(4,5-dihydrothiazol-2-yl)terephthalamide. MS (Q1) 471 (M)+. The product was purified on reverse phase HPLC

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

Procedure: A mixture of 3.8 g of 1-bromo-2-oxo-1,2-di(4-cyanophenyl)ethane, prepared as described above in part (b) and 3.8 g of 2-aminothiazoline in 70 ml of DMF was stirred at room temperature for 18 hours. The reaction mixture was diluted with cold water, and the precipitated product was filtered and dried in vacuum. The material was suspended in 200 ml of toluene, 125 mg of p-toluenesulfonic acid was added, and the mixture was refluxed for 2 hours with removal of water. After cooling, the crude product was filtered and recrystallized twice from acetic acid to afford the part (c) title compound, 1.3 g, m.p. 255°-260°; Analysis: C19H12N4S.0.5AcO; Theory; C 67.03%, H 3.91%, N 15.64%; found C: 67.03% H: 3.96%, N: 15.04%. prepared the precipitated product was filtered dried in vacuum 125 mg of p-toluenesulfonic acid was added the mixture was refluxed for 2 hours with removal of water After cooling the crude product was filtered recrystallized twice from acetic acid