Ethyl 4-amino-2-(methylthio)-5-thiazolecarboxylate

The synthesis of ethyl 4-amino-2-(methylthio)thiazole-5-carboxylate Ethyl 2-mercaptoacetate (5 g, 42 mmol, 1.0 eq) was dissolved in DMF (50 mL) and added with N-thienodi-thioimino carbonate (6.1 g, 42 mmol, 1.0 eq) and DIPEA (16.3 g, 126 mmol, 3.0 eq). After heating at 100 °C for 5 h, the mixture was diluted with saturated aqueous ammonium chloride (100 mL) and extracted with EtOAc (100 mLx2). The combined organic layer was washed with brine, dried, concentrated. The solid was washed with n-hexane and dried under vacuum to give the title compound (8 g, yield: 89percent) as a yellow solid. ESI-MS (M+H)The ethyl bromoacetate (1.96 g, 11.76 mmol) was added to a stirred solution of potassium methyl cyanimidodithiocarbonate 1 (2.0 g, 11.76 mmol) in EtOH (50 mL). The mixture was heated to reflux for 1 h. After cooling, EtGeneral procedure: To asolution of acyclic 1, 3-dicarbonyl compounds 12 (1.0 mmol) in EtOH (3.0 mL) was added NBS (178 mg, 1 mmol). Thereaction mixture was stirred for 10 min (30 min for 12b and 12e) at roomtemperature. Afterwards 7 (1 mmol)was added and the reaction mixture was stirred for another 20 min at roomtemperature. After that, the solvent was evaporated under reducedpressure, and the residue was purified viaa short silica gel column to afford the desired product 11.General procedure: To asolution of acyclic 1, 3-dicarbonyl compounds 12 (1.0 mmol) in EtOH (3.0 mL) was added NBS (178 mg, 1 mmol). Thereaction mixture was stirred for 10 min (30 min for 12b and 12e) at roomtemperature. Afterwards 7 (1 mmol)was added and the reaction mixture was stirred for another 20 min at roomtemperature. After that, the solvent was evaporated under reducedpressure, and the residue was purified viaa short silica gel column to afford the desired product 11.The synthesis of ethyl 4-amino-2-(methylthio)thiazole-5-carboxylate Ethyl 2-mercaptoacetate (5 g, 42 mmol, 1.0 eq) was dissolved in DMF (50 mL) and added with N-thienodi-thioimino carbonate (6.1 g, 42 mmol, 1.0 eq) and DIPEA (16.3 g, 126 mmol, 3.0 eq). After heating at 100 °C for 5 h, the mixture was diluted with saturated aqueous ammonium chloride (100 mL) and extracted with EtOAc (100 mLx2). The combined organic layer was washed with brine, dried, concentrated. The solid was washed with n-hexane and dried under vacuum to give the title compound (8 g, yield: 89percent) as a yellow solid. ESI-MS (M+H)The ethyl bromoacetate (1.96 g, 11.76 mmol) was added to a stirred solution of potassium methyl cyanimidodithiocarbonate 1 (2.0 g, 11.76 mmol) in EtOH (50 mL). The mixture was heated to reflux for 1 h. After cooling, EtGeneral procedure: To asolution of acyclic 1, 3-dicarbonyl compounds 12 (1.0 mmol) in EtOH (3.0 mL) was added NBS (178 mg, 1 mmol). Thereaction mixture was stirred for 10 min (30 min for 12b and 12e) at roomtemperature. Afterwards 7 (1 mmol)was added and the reaction mixture was stirred for another 20 min at roomtemperature. After that, the solvent was evaporated under reducedpressure, and the residue was purified viaa short silica gel column to afford the desired product 11.General procedure: To asolution of acyclic 1, 3-dicarbonyl compounds 12 (1.0 mmol) in EtOH (3.0 mL) was added NBS (178 mg, 1 mmol). Thereaction mixture was stirred for 10 min (30 min for 12b and 12e) at roomtemperature. Afterwards 7 (1 mmol)was added and the reaction mixture was stirred for another 20 min at roomtemperature. After that, the solvent was evaporated under reducedpressure, and the residue was purified viaa short silica gel column to afford the desired product 11.

Molecular Weight:218.3
XLogP3:2.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:4
Exact Mass:218.01836991
Monoisotopic Mass:218.01836991
Topological Polar Surface Area:119
Heavy Atom Count:13
Complexity:191
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes