Methyl2-amino-4-methylthiazole-5-carboxylate

white crysta

General 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.General 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 3.3-carbonyl-Butyric acidMethyl ester(I-i) (116mg)And thiourea (II) (152 mg) were added to methanol (5 mL) at room temperature.Add to reactionPeroxy tert-butyl alcohol (288 μL)And azobisisobutyronitrile (33mg), Stirred at reflux temperature for 5 hours. After the reaction is over, it is cooled to room temperature.Saturated aqueous sodium bicarbonate solution (50 mL) was added and extracted with ethyl acetate.The organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude product.The crude product was isolated and purified by column chromatography (ethyl acetate: petroleum ether (v/v) = 3:7).The white solid methyl 2-amino-4-methyl-5-carboxylate thiazole (III-i) (124 mg) was obtained in a yield of 72percent.A solution of amine 2a (0.866 g, 5 mmol) in THF (3 mL) was added dropwise over 20 min to a solution of t-BuONO (0.772 g, 7.5 mmol) and DMSO (39 mg, 0.5 mmol) in THF (7 mL) at 30 C. Subsequently, 2, 2, 6, 6-tetramethylpiperidinyl-1-oxy radical (TEMPO) (780 mg, 5 mmol) was added and the reaction mixture was stirred vigorously at 30 C for 1.5 h. The solvent was evaporated off and the crude product was purified by column chromatography on silica gel (hexane/ethyl acetate = 15:1) to obtain the aryl radical/TEMPO adduct 7 (0.547 g, 35% yield).General procedure: A solution of amine 2 (5 mmol) in THF (3 mL) was added dropwise over 20 min to a solution of t-BuONO (7.5 mmol) and DMSO (0.5 mmol) in THF (7 mL) at 30 C. The mixture was stirred at 30 C until the starting materials 2 were consumed (monitored by TLC). The solvent was evaporated, and the yields of the low boiling point products were determined by GC; the high boiling point products were isolated by column chromatography on silica gel (hexane/ethyl acetate).The amine 2a (0.172 g, 1 mmol) and DMSO (8 mg, 0.1 mmol) were added to an oven dried Schlenck tube. The system was evacuated and filled with argon (three times) before dry d8-THF (0.5 mL) was added, and the reaction mixture was stirred vigorously for 5 min. Then t-BuONO (0.154 g, 1.5 mmol) was added and the stirring was continued at 30 C for 1 h. The solvent was evaporated off and the crude product was purified by column chromatography on silica gel (hexane/ethyl acetate = 8:1) to obtain the deuterated product 3a' (0.147 g, 93% yield).

Used as pharmaceutical intermediate

Molecular Weight:172.21
XLogP3:1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:2
Exact Mass:172.03064868
Monoisotopic Mass:172.03064868
Topological Polar Surface Area:93.4
Heavy Atom Count:11
Complexity:165
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes