Ethyl 2-amino-5-bromothiazole-4-carboxylate

General procedure: 2-Aminothiazoles (0.1 mol) were dissolved in the least amount of glacial acetic acid, and then bromine (0.11 mol) was added drop-wise with continuous stirring at room temperature. The mixture was heated at 80 °C for 90 min then stirred at room temperature for 12 h. The mixture was filtered and washed with water. The precipitate was heated in water, and the aqueous solution was alkalized by ammonia, filtered, washed with water and then dried. Crystals were formed from ethanol/water to give the 5-bromothiazol-2-amine compounds 3a–f.General procedure: 2-Aminothiazoles (0.1 mol) were dissolved in the least amount of glacial acetic acid, and then bromine (0.11 mol) was added drop-wise with continuous stirring at room temperature. The mixture was heated at 80 °C for 90 min then stirred at room temperature for 12 h. The mixture was filtered and washed with water. The precipitate was heated in water, and the aqueous solution was alkalized by ammonia, filtered, washed with water and then dried. Crystals were formed from ethanol/water to give the 5-bromothiazol-2-amine compounds 3a–f.General procedure: 2-Aminothiazoles (0.1 mol) were dissolved in the least amount of glacial acetic acid, and then bromine (0.11 mol) was added drop-wise with continuous stirring at room temperature. The mixture was heated at 80 C for 90 min then stirred at room temperature for 12 h. The mixture was filtered and washed with water. The precipitate was heated in water, and the aqueous solution was alkalized by ammonia, filtered, washed with water and then dried. Crystals were formed from ethanol/water to give the 5-bromothiazol-2-amine compounds 3a-f.2-Amino-thiazole-4-carboxylic acid ethyl ester (1.4 g, 8 mmol) is dissolved in acetonitrile (15 ml) and N-bromosuccinimide. (1.7 g, 9.6 mmol, 1.2 equiv.) was added in one portion. The mixture was stirred at room temp. for 3 hours, then filtered and the filtrate was evaporated. After purification on silica-gel with ethyl acetate/n-heptane as eluent, 0.71 g of an off-white solid were obtained: MS: m/e 248.9 (M-H).Example 39; 4-Ethoxycarbonyl-5-(2-trimethylsilylethynyl)thiazole; a) 2-Amino-5-bromo-4-ethoxycarbonylthiazole; In the same manner as in step a) in Example 1, 46.27 g of 2-amino-5-bromo-4-ethoxycarbonylthiazole was prepared from 43.05 g of 2-amino-4-ethoxycarbonylthiazole and 48.95 g of N-bromosuccinimide. NMR (CDCl3) delta: 1.39 (3H, t, J=7.1 Hz), 4.36 (2H, q, J=7.1 Hz), 6.05 (H, br s)General procedure: A mixture of 2-aminothiazole derivatives 2a-h and 3a-e (1.0 mmol) and K2CO3 (4.0 mmol) was stirred at room temperature with drop-wise addition of 4-chlorobutyryl chloride (4.0 mmol) in chloroform for 48 h. The reaction mixture was monitored by TLC (using chloroform/ethyl acetate 9:1). Ammoniated water was added, and the organic layer was separated and dried over anhydrous Na2SO4, and the solvent was removed in vacuum. The resulting precipitate was crystallized from ethanol to give crystals of pure N-(thiazole-2-yl)-4-chlorobutanamide derivatives.

Molecular Weight:251.10
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:249.94116
Monoisotopic Mass:249.94116
Topological Polar Surface Area:93.4
Heavy Atom Count:12
Complexity:181
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes