Ethyl2-amino-4-methylthiazole-5-carboxylate

off-white powder

200 ml of 25percent ethyl acetate in ethanol was added to the four-necked bottle, 30.4 g of thiourea, 1.5 g of sodium carbonate were added, and the temperature was raised to 45 ° C.33 g of ethyl 2-chloroacetoacetate was added dropwise, and the mixture was added dropwise over 20 to 30 minutes. The temperature was raised to 65 ° C for 5 hours, and most of the solvent was distilled off under normal pressure and then cooled to room temperature.The unreacted thiourea was removed by filtration, the filtrate was added to 500 ml of water, and the pH was adjusted to 9-10 with 30percent liquid alkali, and stirred for 0.5 h.After suction filtration and vacuum drying for 2 hours, the product was 36.7 g, and the yield was 98.39percent.The 11.3 g, 84 mmol of thionyl chloride was added dropwise over 30 minutes previously cooled to 0 ° C containing 10 g, 76.9mmol of ethyl acetoacetate in 100 ml methylene chloride solution. After completion of stirring at room temperature overnight, thereaction solution respectively saturated sodium bicarbonate and saturated sodium chloride solution, the organic layer wascollected, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 12.4 g of pink oil of ethyl 3-acetyl VII chloroacetate, 98.4percent yield, 3- acetyl acid ethyl ester VII prepared by the amount corresponding scaled up or down thevolume of the reaction vessel according to the corresponding scaled up or down, a commercially available compound VII havethe same effect; in 100 ml round-bottomed flask, 40 ml of ethanol and thiourea 2.0 g, 33.5 mmol, stirred and heated to refluxthiourea dissolved, add 5.5 g, 33.5 mmol 3- acetyl acid ethyl ester VII, after reflux overnight and concentrated under reducedpressure to remove ethanol to give a yellow solid, saturated with carbonate after filtration and washing soda solution of 5.3 g of2-amino-4-methyl-5-ethyl thiazole VIII, a yield of 91.4percent, 2-amino-4-methyl-5-ethyl thiazole VIII prepared by the amountcorresponding scaled up or down the volume of the reaction vessel according to the corresponding scaled up or down, acommercially available compound VII have the same effect.In anhydrous ethanol (100 mL), thiourea (0.098 M) was added and stirred at room temperature. To this solution ethyl-2-chloro acetoacetate (0.097 M) was added dropwise under constant stirring at room temperature. Once addition of ethyl-2-chloro acetoacetate is complete, reaction mixture was heated at 70-80°C for 15 min. Then reaction mass was cooled to room temperature and the solid precipitate was isolated, washed with 100 mL of ethanol and further washed with saturated sodium bicarbonate solution to obtain white solid which was finally dried under vacuum at 50°C for 8 h Yield: 91percent; m.p.: 170-174°C; IR (KBr v max): 3357, 3055, 1741, 1680 1492, 1388, 913, 728 cmTo a solution of 2-chloro-3-oxo-butyric acid ethyl ester (5 g, 0.030 mol, 1 eq) in ethanol (25 mL) was added thiourea (2.55 g, 0.033 mmol, 1.1 eq) at 25 °C, and the reaction mixture was heated at reflux for 3 h. Then reaction mixture was gradually cooled to 25 °C with stirring to precipitate the product as a white solid. The precipitated solid was collected by filtration using a Buckner funnel and dried under vacuum to obtain ethyl 2-amino-4- methylthiazole-5-carboxylate (4.8 g, 64percent) as a fine white powder.Step; 1 Preparation of ethyl 2-amino-4-methyl-l, 3-thiazoIe-5-carboxylateTo a solution of 2-chloro-ethyl acetoacetate (0.82g, 5mmol) in EtOH (25ml) was added thiourea (0.38gm, 5mmol) and the reaction mixture was stirred for 5 minutes at 3OTo a stirred solution of ethyl 2-chloroacetoacetate (6.0 mL, 43.35 mmol) in MeCN (24 mL) and THF (6 mL) was added thiourea (3.0 g, 39.41 mmol) and NaGeneral procedure: A mixture of methylcarbonyl (0.5 mmol), thiourea (0.5 mmol), iodine (0.5 mmol), DMSO (2 mL) and 20 mg MMT-K10 was stirred at 80 °C. After completion of the reaction (monitored by TLC, petroleum:ethyl acetate, 4:1), the catalyst was separated by filtration, and then the solvent was removed under reduced pressure. The crude product was dissolved in hot water, extracted with ether (3 9 30 mL), and adjusted to pH = 9–10 by ammonia to give the solid products. Finally, the resulting precipitate was recrystallyzed by EtOH.General procedure: A mixture of methylcarbonyl (0.5 mmol), thiourea(0.5 mmol), iodine (0.5 mmol), DMSO (2 mL) and 10 mgStarch NPs were stirred at 80 C. After completion of thereaction (monitored by TLC, petroleum:ethyl acetate, 4:1), the reaction was quenched by the addition of 10 mL distilledwater. The aqueous solution was extracted withEtOAc (3 9 10 mL) and the combined extract was driedwith anhydrous Na2SO4. The solvent was vacuumed, andfinally, the resulting precipitate was recrystallized byEtOH.General procedure: A mixture of methyl carbonyl (2 mmol), thiourea (3 mmol), NIS(2 mmol), and NH2-MMT (0.10 g) in EtOH (5 mL) at room temperature was stirred until completion of reaction. The progress of the reaction was monitored by TLC (petroleum ether-ethyl acetate 4:1). After completion of the reaction, the NH2-MMT was separated by filtration. After evaporation of EtOH under vacuum, the crude product was dissolved in boiling water and adjusted to pH 8 withthe amount of ammonia to give the solid products. The solid obtained was recrystallized from a mixture of ethanol-water.To a 50 ml round bottom flask was added 20 ml of water, Then will be 1.5mmo 1 of the sulfonated cup [6] is added to the round bottom flaskAnd stir to make it completely soluble in water, To obtain a sulfonated cup [6] aqueous solution;3 mmol of ethyl acetoacetate was dissolved in 2 ml of acetone and mixed well, To give the mixture N1; the mixture N1 was slowly dropped into the sulfonated cup [6] aromatic aqueous solution at a rate of 60 drops / min, Followed by the addition of 0.03 mmol of N-bromosuccinimide and 3 mmo of thiourea at 20 ° C for lh;Finally, the reaction mixture was successively extracted by ethyl acetate, dried over anhydrous sodium sulfate, Vacuum distillation and column chromatography (mobile phase ethyl acetate: petroleum ether = 1:10, stationary phase silica gel)Get 52gAmine thiazole pentad heterocyclesCompoundsA1, The yield was 93percentGeneral procedure: A mixture of the acetophenone (2 mmol), thiourea (3 mmol) and iodine (2 mmol), in the presence of 0.03 g nanochitosan was refluxed in EtOH. General procedure: General procedure: The substrate 1 (1.0 mmol) and thiourea 2(2.0 mmol) were added to solvent (5 mL methanol) at room tem-perature. To the reaction mixture, TBHP (3.0 mmol) and AIBN(0.2 mmol) were added respectively. The reaction mixture wasstirred at room temperature (for substrates 1a-f) or reux tem-perature (for substrates 1g-r) until TLC indicated the total consumption of 1 (for substrates 1p-q, the reaction time is 24 h).The residue was treated with saturated aqueous NaHCO3 (50 mL)and then extracted with EA (30 mL 3). The organic phase waswashed with brine (50 mL 1), dried over anhydrous Na2SO4. Thesolvent was removed and the residue was puried by ash columnchromatography on silica gel (EA/PE) to afford the desired compound 3.General procedure: To a solution of the appropriate β-keto ester (1 mmol) in H2O (5 mL)held at 70 °C was added TBCA (146 mg, 0.4 mmol) in small portions and the mixture was stirred at 70 °C for 20 min. Then, MeCN (5 mL), the respective thiourea (1 mmol), and DABCO (1 mmol) were successively added and the mixture was stirred at 70 °C for an additional 20min. After the completion of the reaction, the mixture was poured onto ice and the precipitated solid was collected by filtration to afford the corresponding pure 2-aminothiazole 1.EXAMPLE 22A

Molecular Weight:186.23
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:186.04629874
Monoisotopic Mass:186.04629874
Topological Polar Surface Area:93.4
Heavy Atom Count:12
Complexity:177
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes