2-Amino-4-methylthiazole-5-carboxylic acid

To a solution of ethyl 2-amino-4-methyl-1, 3-thiazole-5-carboxylate 5 (3.00g, 16.1mmol) in ethanol (100mL) was added 1M sodium hydroxide solution (50.0mL) at room temperature, and the mixture was stirred for 26h. After the volatiles of the mixture were removed in vacuo, water and acetic acid were added to the residue to adjust the pH to 5.0. The resulting precipitate was collected by filtration, washed with water, and dried in vacuo to yield 6 (2.48g, 97percent) as a colorless powder. A. A mixture of ethyl 2-amino-4-methylthiazole-5-carboxylate (6.58 g, 35.5 mmol) and NaOH (5.40 g, 135.0 mmol) in tetrahydrofuran (60 mL) and water (30 mL) was heated to reflux overnight. Tetrahydrofuran was removed in vacuo, and the residue was neutralized with 5percent hydrochloric acid solution to pH 5~6. The precipitate obtained was collected by filtration and dried to afford the crude 2-amino-4-methylthiazole-5- carboxylic acid (5.20 g, 94percent): PREPARATION 1; Preparation of 2-amino-7V-benzyl-4-methylthiazole-5-carboxamide; A. A mixture of ethyl 2-amino-4-methylthiazole-5-carboxylate (6.58 g, 35.5 mmol) and NaOH (5.40 g, 135 mmol) in tetrahydrofuran (60 mL) and water (30 mL) was heated to reflux overnight. Tetrahydrofuran was removed in vacuo, and the residue was The thiazole ethyl ester (1.0 g, 5.81 mmol) was treated with 0.5 M ethanolic sodium hydroxide solution (60 mL), overnight at room temperature. The reaction mixture was then cooled in an ice bath, and neutralized with acetic acid. The precipitated acid 2 was filtered, washed with diethyl ether, and dried overnight at 60 °C.Yield: 81percent; off-white crystals, mp 225-227 C (lit. [31] 223 °C). 1HNMR (400 MHz, DMSO-d6): 2.35 (s, 3H, CH3), 7.61 (s, 2H, NH2), 12.26(br s, 1H, COOH) ppm. HRMS (ESI): m/z [M H] calcd forC5H7N2O2S 159.1698; found 159.1663.Ethyl 2-amino-4-methyl-1, 3-thiazole-5-carboxylate(2) (0.075 M) and sodium hydroxide (0.3 M) in methanol were taken in 50 mL round bottom flask. The solution was refluxed with stirring until the reaction was complete. The clear solution was cooled and neutralized with glacial acetic acid and stirred for 30 min. Precipitate obtained was filtered, washed with water, dried and recrystallized with ethanol. The progress of the reaction and purity of the compound were checked by TLC, using benzene : acetone (8 : 2) as mobile phase. Yield: 79percent; m.p.: 160-162°C; IR (KBr v max) : 3370, 3055, 1741, 1645, 1492, 1388, 913, 728 cmA. To a solution of ethyl 2-amino-4-methylthiazole-5-carboxylate (2.19 g, 11.8 mmol) in a 1 :1 mixture of tetrahydrofuran (20 mL) and water (10 mL) was added sodium hydroxide (1.80 g, 45.0 mmol). The reaction mixture was refluxed for 18 hours and allowed to cool down to ambient temperature. The organic solvent was removed in vacuo. The aqueous solution was acidified with 10percent aqueous hydrochloric acid solution. The colorless solid was collected and dried to afford 2-amino-4-methylthiazole-5- carboxylic acid (1.40 g, 75percent):

Molecular Weight:158.18
XLogP3:0.9
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:1
Exact Mass:158.01499861
Monoisotopic Mass:158.01499861
Topological Polar Surface Area:104
Heavy Atom Count:10
Complexity:153
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes