4-(3-Chloro-phenyl)-thiazol-2-ylamine

General procedure: A mixture of thiourea (50 mmol), the corresponding acetophenone (25 mmol) and iodine (25 mmol) is stirred at 100 °C for 8 h.Then the reaction mixture is cooled, extracted with diethyl ether toremove excess of acetophenone, and then washed with aqueous sodium thiosulfate to remove excess iodine and later with cold water. The crude product is dissolved in hot water, filtered to remove sulphone, and the filtrate is basified with aqueous Na2CO3to yield the corresponding 2-amino-4-(substituted-phenyl)-1, 3-thiazole. The crude product is purified by recrystallization from alcohol.In a 25 mL reaction flask, add 3 mL of water and 30 μL of Tween, 0.5mmol of m-chlorostyrene and 0.75mmol of DBH reacted at 60°C for 1h.After the reaction was completed, the water was swirled, 3 mL of ethanol was added, and 0.75 mmol of thiourea was added. The reaction was refluxed for 1 h. After the reaction was completed, ethanol was spin-dried, and ethyl acetate was added to dissolve the solution.The mixture was extracted with saturated brine, and the organic layer was concentrated. Column chromatography gave 85 mg of a white solid with a yield of 81percent.Step 2: To a mixture of 2-bromo-1-(3-chlorophenyl)ethan-1-one (0.5 g, 2.1 mmol) and thiourea (0.2 g, 2.3 mmol) in anhydrous EtOH (5 mL) was heated at reflux for 1 h. After that, the solvent was removed in vacuo, and saturated aqueous NaHCOTo a solution of 2-bromo-1-(3-chlorophenyl)ethanone (28 g) in ethanol (300 ml) was added thiourea (10.04 g). The reaction mixture was refluxed overnight. Solvent was removed, and the residue was triturated with diethyl ether to give the title compound (23 g) as a white solid. MS(ESGeneral procedure: A mixture of the substrate (i.e. appropriate bromoketone) (1 eq) and thiourea (1.5 eq) in EtOH (3 mL per 1 mmol of bromoketone, unless stated otherwise) was refluxed for 2 h (unless stated otherwise). (0082) Work-up 1: (0083) A saturated aqueous solution of NaHCCE (3 mL per 1 mmol of bromoketone) was added to the mixture, which was then extracted with EtOAc (3 x 5 mL per 1 mmol of bromoketone). The combined organic extracts were washed with brine (3 mL per 1 mmol of bromoketone), dried over MgS04, filtered, and the solvent was evaporated in vacuo. If necessary, the product was purified by column chromatography on silica gel (unless stated otherwise) to provide the desired aminothiazole. (0084) Work-up 2: (0085) The solvent was evaporated in vacuo. The resulting solid was triturated with EtOAc (1 mL per 1 mmol of bromoketone) and the mixture was filtered. The solid residue was dissolved in MeOH (1 mL per 1 mmol of bromoketone). A saturated aqueous solution of NaHCOs (3 mL per 1 mmol of bromoketone) was added and the mixture was extracted with EtOAc (3 x 5 mL per 1 mmol of bromoketone). The combined organic extracts were washed with brine (3 mL per 1 mmol of bromoketone), dried over MgS04, filtered, and the solvent was evaporated in vacuo. The product - the desired aminothiazole - was usually sufficiently pure and was used directly without further purification (unless stated otherwise) in the next step.General procedure: To a solution of the appropriate aminothiazole (1 eq) in anhydrous THF:MeOH (5:1) (6 inL per 1 mmol, unless stated otherwise), was added NaH (1.1 eq, 60% in mineral oil) at 0 C. The mixture was stirred at 55 C and ethyl cyanoacetate (1.5 eq) was added. After 4 h, additional ethyl cyanoacetate (1.5 eq) was added and the mixture was refluxed for 14 h. The mixture was cooled to 25 C, a saturated aqueous solution of NH4CI (20 inL per 1 mmol of aminothiazole) was added and the mixture was extracted with EtOAc (3 x 20 inL per 1 mmol of aminothiazole). Organic phases were combined and washed with brine (20 inL per 1 mmol of aminothiazole), dried over MgS04, filtered, and the solvent was evaporated in vacuo. The residue was purified by column chromatography to provide the desired cyanoacetamide.Add 3 mL of water and 30 muL of Tween in a 25 mL reaction flask. 0.50 mmol of 1-chloro-3-ethylbenzene, 1.50 mmol of NBS and 0.05 mmol of AIBN were reacted at 60 C for 4 h, and then cooled after completion of the reaction. Then add 1.50 mmol of sodium bicarbonate and 0.50 mmol of thiourea in sequence. After reacting at 80 C for 1 h, ethyl acetate was added after the reaction. Extracted with saturated brine and concentrated organic phase. Column chromatography gave 90 mg of a white solid in a yield of 86%.Add 3 mL of water to a 25 mL reaction flask, and then add 0.50 mmol of 1-chloro-3-ethylbenzene and 0.75 mmol of DBH.And 0.05mmol TBHP, reacted at 60 C for 4h, after cooling, then add 1.50mmol sodium bicarbonate and 0.50mmol thiourea, The reaction was continued at 80 C for 1 h, and after completion of the reaction, ethyl acetate was added for extraction, and the organic phase was concentrated and purified by column chromatography.79 mg of a white solid in a yield of 75%.In a 25 mL reaction flask, add 3 mL of water and 30 muL of Tween, 0.5mmol of m-chlorostyrene and 0.75mmol of DBH reacted at 60C for 1h.After the reaction was completed, the water was swirled, 3 mL of ethanol was added, and 0.75 mmol of thiourea was added. The reaction was refluxed for 1 h. After the reaction was completed, ethanol was spin-dried, and ethyl acetate was added to dissolve the solution.The mixture was extracted with saturated brine, and the organic layer was concentrated. Column chromatography gave 85 mg of a white solid with a yield of 81%.General procedure: The benzo [1, 3] dioxol-5-yl-cyclopropanecarboxylic acid (1 eq) was resuspended in anhydrous DMF (1ml), HBTU (1 eq) and DIPEA (1 eq) were added. The reaction was vigorously stirred for 5min and the appropriate thiazole or aminic derivative (1 eq) in anhydrous DMF (500muL) was added, and the reaction was kept at T=40C until completeness (from 14h to 24h) depending from reactants. The mixture was concentrated under vacuum and after extraction with organic solvent (3×3ml), washed with H2O (3×2ml). The organic phases were dried over Na2SO4 and concentrated under reduced pressure and concentrated under vacuum. The crude product was then purified by preparative HPLC; the peak of interest was concentrated in vacuum and finally lyophilized to obtain the final compound.General procedure: The benzo [1, 3] dioxol-5-yl-cyclopropanecarboxylic acid (1 eq) was resuspended in anhydrous DMF (1ml), HBTU (1 eq) and DIPEA (1 eq) were added. The reaction was vigorously stirred for 5min and the appropriate thiazole or aminic derivative (1 eq) in anhydrous DMF (500muL) was added, and the reaction was kept at T=40C until completeness (from 14h to 24h) depending from reactants. The mixture was concentrated under vacuum and after extraction with organic solvent (3×3ml), washed with H2O (3×2ml). The organic phases were dried over Na2SO4 and concentrated under reduced pressure and concentrated under vacuum. The crude product was then purified by preparative HPLC; the peak of interest was concentrated in vacuum and finally lyophilized to obtain the final compound.

Molecular Weight:210.68
XLogP3:2.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:210.0018471
Monoisotopic Mass:210.0018471
Topological Polar Surface Area:67.2
Heavy Atom Count:13
Complexity:179
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes